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1.
Behav Pharmacol ; 33(1): 32-41, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35007234

RESUMO

Epigallocatechin-3-gallate (EGCG) and caffeine are the two primary compounds found in green tea. While EGCG has anxiolytic and anti-inflammatory effects, its acute effects on cognition are not well understood. Furthermore, despite widespread green tea consumption, little is known about how EGCG and caffeine co-administration impacts behavior. Here, we investigated the effects of multiple doses of either EGCG or caffeine on a rat model of risk-taking. This was assessed using the risky decision-making task (RDT), in which rats choose between a small, well-tolerated reward and a large reward with escalating risk of mild footshock. Rats were tested in RDT after acute systemic administration of EGCG, caffeine or joint EGCG and caffeine. EGCG caused a dose-dependent reduction in risk-taking without affecting reward discrimination or task engagement. Caffeine did not impact risk-taking, but elevated locomotor activity and reduced task engagement at high doses. Finally, exposure to both EGCG and caffeine had no effect on risk-taking, suggesting that low-dose caffeine is sufficient to mask the risk-aversion caused by EGCG. These data suggest EGCG as a potential therapeutic treatment for psychological disorders that induce compulsive risky decision-making.


Assuntos
Cafeína/farmacologia , Catequina/análogos & derivados , Cognição/efeitos dos fármacos , Comportamento Compulsivo/induzido quimicamente , Tomada de Decisões/efeitos dos fármacos , Assunção de Riscos , Chá , Animais , Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Catequina/farmacologia , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Locomoção/efeitos dos fármacos , Modelos Animais , Psicotrópicos/farmacologia , Ratos , Chá/efeitos adversos , Chá/química
2.
Int J Biol Markers ; 36(2): 57-63, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34027694

RESUMO

PURPOSE: Genomic signatures, such as EndoPredict®, may help clinicians to decide which adjuvant treatment is the most appropriate. METHODS: We propose the EndoPredict® assay for unclear cases of adjuvant treatment in patients treated in our comprehensive cancer center. We prospectively and retrospectively report the decision of adjuvant treatment before and after the EndoPredict® assay, respectively, compared to the PREDICT's tool scores. RESULTS: From November 2016 to March 2019, 159 breast cancer tumors were analyzed and presented before and after the EndoPredict® assay. Before the EndoPredict® results, clinicians recommended chemotherapy for 57 patients (57/159, 36%). A total of 108 patients (108/159, 68%) were classified as EPclin high-risk score. There was only a slight agreement between clinicians' decisions and EPclin risk score. The EPclin score led to 37% changes in treatment (59/159); chemotherapy was favored in 80% of cases (47/59). The PREDICT tool recommended chemotherapy for 16 high-risk patients (16/159, 10%). CONCLUSION: Although genomic tests were developed in order to de-escalate adjuvant treatment, in our comprehensive cancer center the use of the EndoPredict® assay led to an increase in prescribed chemotherapy.


Assuntos
Quimioterapia Adjuvante/métodos , Tomada de Decisões/efeitos dos fármacos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Adulto Jovem
3.
PLoS One ; 15(2): e0229294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32084218

RESUMO

Catecholamines have long been associated with cognitive control and value-based decision-making. More recently, we have shown that catecholamines also modulate value-based decision-making about whether or not to engage in cognitive control. Yet it is unclear whether catecholamines influence these decisions by altering the subjective value of control. Thus, we tested whether tyrosine, a catecholamine precursor altered the subjective value of performing a demanding working memory task among healthy older adults (60-75 years). Contrary to our prediction, tyrosine administration did not significantly increase the subjective value of conducting an N-back task for reward, as a main effect. Instead, in line with our previous study, exploratory analyses indicated that drug effects varied as a function of participants' trait impulsivity scores. Specifically, tyrosine increased the subjective value of conducting an N-back task in low impulsive participants, while reducing its value in more impulsive participants. One implication of these findings is that the over-the-counter tyrosine supplements may be accompanied by an undermining effect on the motivation to perform demanding cognitive tasks, at least in certain older adults. Taken together, these findings indicate that catecholamines can alter cognitive control by modulating motivation (rather than just the ability) to exert cognitive control.


Assuntos
Catecolaminas/metabolismo , Cognição/fisiologia , Voluntários Saudáveis , Idoso , Cognição/efeitos dos fármacos , Tomada de Decisões/efeitos dos fármacos , Feminino , Humanos , Comportamento Impulsivo/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Tirosina/farmacologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-31811876

RESUMO

Maladaptive decision making is a characteristic feature of substance use disorder and pathological gambling. Studies in humans and animals have implicated neural circuits that include the basolateral amygdala (BLA) and nucleus accumbens (NAc) in facilitating risk/reward decision making. However, the preclinical literature has focussed primarily on situations where animals use internally-generated information to adapt to changes in reward likelihood, whereas many real-life situations require the use of external stimuli to facilitate context-appropriate behavior. We recently developed the "Blackjack" task, to measure cued risk/reward decision making requiring rats to chose between Small/Certain and Large/Risky rewards, with auditory cues at the start of each trial explicitly informing that the probability of obtaining a large reward was either good (50%) or poor (12.5%). Here we investigated the contribution of the BLA and its interaction with the NAc in guiding these types of decisions. In well-trained male rats, bilateral inactivation of the BLA induced suboptimal decision making, primarily by reducing risky choice on good-odds trials. In comparison, pharmacological disconnection of the BLA and NAc-shell also induced suboptimal decision making, diverting choice from more preferred option by reducing or increasing risky choice on good vs. poor odds trials respectively. Together, these results suggest that the BLA-NAc circuitry plays a crucial role in integrating information provided by discriminative stimuli. Furthermore, this circuitry may aid in guiding action selection of advantageous options in situations to maximize rewards. Finally, they suggest that perturbations in optimal decision making observed in substance abuse and gambling disorders may be driven in part by dysfunction within this circuitry.


Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiologia , Tomada de Decisões/fisiologia , Rede Nervosa/fisiologia , Núcleo Accumbens/fisiologia , Recompensa , Assunção de Riscos , Estimulação Acústica , Agonistas alfa-Adrenérgicos/farmacologia , Anestésicos Dissociativos/farmacologia , Animais , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Condicionamento Operante , Sinais (Psicologia) , Tomada de Decisões/efeitos dos fármacos , Discriminação Psicológica , Jogo de Azar , Ketamina/farmacologia , Masculino , Rede Nervosa/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Ratos , Ratos Long-Evans , Xilazina/farmacologia
5.
Nutrients ; 11(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581523

RESUMO

Cognitive function is critical for successful prolonged performance in eSports. This double-blind placebo-controlled study examined the effect of an inositol-enhanced arginine silicate oral supplement on cognitive performance and energy in eSports athletes. Sixty healthy men and women who spent 5 or more hours a week playing video games were randomly assigned to take supplement or placebo for 7 days. On day 1 and 7, before and 15 min after dosing, subjects completed the Trail Making Test (TMT), Parts A and B; Stroop Test; and Profile of Mood States (POMS) questionnaire, and then played a video game for 60 min. Immediately after, cognitive tests were repeated. Self-reported energy levels increased, anger decreased, and TMT-B test errors decreased in the supplement group compared to placebo (p < 0.05). Fatigue, TMT-B time, and TMT B-A score improved in the supplement group compared to baseline (p < 0.05). After 60 min of gaming, supplementation decreased Stroop Test errors and TMT-A time (p < 0.05). Adverse events were minimal and not different between groups. These data appear to support the use of the studies product (nooLVL®) in eSports gamers looking to improve their accuracy, decision making, and reaction time during gaming.


Assuntos
Afeto/efeitos dos fármacos , Arginina/administração & dosagem , Cognição/efeitos dos fármacos , Suplementos Nutricionais , Inositol/administração & dosagem , Saúde Mental , Estado Nutricional , Silicatos/administração & dosagem , Jogos de Vídeo/psicologia , Administração Oral , Adulto , Arginina/efeitos adversos , Tomada de Decisões/efeitos dos fármacos , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Inositol/efeitos adversos , Masculino , Missouri , Testes Neuropsicológicos , Estudos Prospectivos , Tempo de Reação/efeitos dos fármacos , Silicatos/efeitos adversos , Análise e Desempenho de Tarefas , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
6.
Brain Res Bull ; 139: 182-189, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29501800

RESUMO

After sustaining a traumatic brain injury (TBI), a person's ability to make daily decisions can be affected. Simple tasks such as, deciding what to wear are no longer effortless choices, but are instead difficult decisions. This study explored the use of a discrimination task with a magnesium treatment in order to examine how decision-making skills are affected after TBI and if the treatment helped to attenuate cognitive and motor impairments. Thirty-one male rats were separated into MAG/TBI, VEH/TBI, or VEH/Sham groups. Pre-TBI, rats were trained to dig in the sand for a reinforcer. After establishment of consistent digging behavior rats received a bilateral frontal cortex injury. Rats received either an i.p. injection of 2 mmol/kg magnesium chloride or control at 4, 24, 72 h post-surgery. Dig task testing began 7 days post-injury, lasting for 4 weeks. The discriminations included two scent pairings; basil (baited) versus coffee then the reversal and then cocoa (baited) versus cumin then the reversal. The results indicated that the magnesium treatment was successful at attenuating cognitive and motor deficits after TBI. The results also indicated that the dig task is a sufficient operant conditioning task in the assessment of frontal functioning after TBI.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/fisiopatologia , Condicionamento Operante/efeitos dos fármacos , Tomada de Decisões/efeitos dos fármacos , Cloreto de Magnésio/uso terapêutico , Análise de Variância , Animais , Lesões Encefálicas Traumáticas/patologia , Discriminação Psicológica/efeitos dos fármacos , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Olfato/efeitos dos fármacos
7.
Eur Neuropsychopharmacol ; 27(12): 1268-1280, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29100819

RESUMO

Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders. Until the recent discovery of the rapid onset antidepressant action of ketamine, pharmacological treatments for MDD were limited to conventional antidepressant drugs with delayed clinical efficacy. Using a judgement bias task, this study has investigated whether the temporal differences observed in patients would be reflected in affective biases and decision making behaviour in rodents. The diffusion model was also used to investigate the underlying decision making processes. Positive biases were induced in this task over timeframes that mirror the rapid versus delayed antidepressant efficacy of the drugs in clinical populations. Diffusion modelling revealed that the antidepressants tested also have different effects on decision making processes, suggesting they may act through different neurobiological substrates. This combination of behaviour and computational modelling may provide a useful approach to further investigate the mechanisms underlying rapid antidepressant effect and assess potential new treatments.


Assuntos
Antidepressivos/uso terapêutico , Aprendizagem por Associação/efeitos dos fármacos , Tomada de Decisões/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Tempo de Reação/efeitos dos fármacos , Estimulação Acústica , Anfetamina/farmacologia , Analgésicos/farmacologia , Animais , Antidepressivos/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Cocaína/farmacologia , Condicionamento Clássico/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/farmacologia , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Ketamina/farmacologia , Masculino , Modelos Biológicos , Fenciclidina/farmacologia , Ratos , Fatores de Tempo
8.
Psychopharmacology (Berl) ; 234(20): 3091-3104, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28733811

RESUMO

RATIONALE: Adding reward-concurrent cues to a rat gambling task (rGT) increases risky choice. This cued version of the task may reflect an "addiction-like" cognitive process, more similar to human gambling than the uncued task. Serotonergic drugs that target 5-HT2 receptors alter mechanisms linked to impulse control. However, relatively little is known regarding the impact of such agents on either risky decision making, or the ability of conditioned stimuli to bias the choice process, despite potential relevance to addiction development and treatment. OBJECTIVES: The aim of this study was to determine the effects of SB 242,084 and M100907, selective antagonists at the 5-HT2C and 5-HT2A receptors respectively, as well as the selective 5-HT2C receptor agonist Ro-60-0175, on performance of both cued and uncued versions of the rGT. RESULTS: SB 242,084 significantly and dose-dependently increased choice of the most optimal option in the cued rGT only, despite concurrently increasing impulsive responses made prematurely on both the cued and uncued rGT. M100907 and Ro-60-0175 did not alter risky decision making, but nevertheless produced the expected decrease in premature responses on both task variants. CONCLUSIONS: These findings demonstrate that the 5-HT2 receptor-mediated regulation of risky decision making and motor impulsivity can be pharmacologically dissociated and further show that the presence of highly salient reward-paired cues critically alters the neurochemical regulation of the choice process. Importantly, these results suggest that 5-HT2C receptor antagonists may be of use in disrupting maladaptive patterns of decision making.


Assuntos
Sinais (Psicologia) , Tomada de Decisões/efeitos dos fármacos , Jogo de Azar/psicologia , Receptor 5-HT2C de Serotonina , Recompensa , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Estimulação Acústica/métodos , Animais , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Tomada de Decisões/fisiologia , Relação Dose-Resposta a Droga , Etilaminas/farmacologia , Indóis/farmacologia , Masculino , Estimulação Luminosa/métodos , Ratos , Ratos Long-Evans , Receptor 5-HT2C de Serotonina/fisiologia
9.
Neurosci Bull ; 33(4): 413-422, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28585114

RESUMO

The thalamus and central dopamine signaling have been shown to play important roles in high-level cognitive processes including impulsivity. However, little is known about the role of dopamine receptors in the thalamus in decisional impulsivity. In the present study, rats were tested using a delay discounting task and divided into three groups: high impulsivity (HI), medium impulsivity (MI), and low impulsivity (LI). Subsequent in vivo voxel-based magnetic resonance imaging revealed that the HI rats displayed a markedly reduced density of gray matter in the lateral thalamus compared with the LI rats. In the MI rats, the dopamine D1 receptor antagonist SCH23390 or the D2 receptor antagonist eticlopride was microinjected into the lateral thalamus. SCH23390 significantly decreased their choice of a large, delayed reward and increased their omission of lever presses. In contrast, eticlopride increased the choice of a large, delayed reward but had no effect on the omissions. Together, our results indicate that the lateral thalamus is involved in decisional impulsivity, and dopamine D1 and D2 receptors in the lateral thalamus have distinct effects on decisional impulsive behaviors in rats. These results provide a new insight into the dopamine signaling in the lateral thalamus in decisional impulsivity.


Assuntos
Tomada de Decisões/fisiologia , Comportamento Impulsivo/fisiologia , Receptores de Dopamina D1/metabolismo , Tálamo/metabolismo , Animais , Benzazepinas/farmacologia , Tomada de Decisões/efeitos dos fármacos , Desvalorização pelo Atraso/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Substância Cinzenta/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Comportamento Impulsivo/efeitos dos fármacos , Imageamento por Ressonância Magnética , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Salicilamidas/farmacologia , Tálamo/efeitos dos fármacos , Fatores de Tempo
10.
Soc Cogn Affect Neurosci ; 12(3): 427-435, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-27664999

RESUMO

Rules, whether in the form of norms, taboos or laws, regulate and coordinate human life. Some rules, however, are arbitrary and adhering to them can be personally costly. Rigidly sticking to such rules can be considered maladaptive. Here, we test whether, at the neurobiological level, (mal)adaptive rule adherence is reduced by oxytocin-a hypothalamic neuropeptide that biases the biobehavioural approach-avoidance system. Participants (N = 139) self-administered oxytocin or placebo intranasally, and reported their need for structure and approach-avoidance sensitivity. Next, participants made binary decisions and were given an arbitrary rule that demanded to forgo financial benefits. Under oxytocin, participants violated the rule more often, especially when they had high need for structure and high approach sensitivity. Possibly, oxytocin dampens the need for a highly structured environment and enables individuals to flexibly trade-off internal desires against external restrictions. Implications for the treatment of clinical disorders marked by maladaptive rule adherence are discussed.


Assuntos
Comportamento Cooperativo , Ocitocina/farmacologia , Conformidade Social , Responsabilidade Social , Administração Intranasal , Adulto , Caráter , Tomada de Decisões/efeitos dos fármacos , Tomada de Decisões/fisiologia , Método Duplo-Cego , Feminino , Humanos , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiopatologia , Masculino , Ocitocina/administração & dosagem , Ocitocina/fisiologia , Recompensa , Inquéritos e Questionários
11.
Physiol Behav ; 167: 238-247, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27650920

RESUMO

Toxins and nutrients interact and define herbivores' experiences with toxic plants. However, there are still open questions about the mechanisms by which nutrient-toxin interactions affect experience and as a consequence foraging decisions by consumers. This study provides a deeper insight into such mechanisms by using supplemental nutrients, a toxic plant typically avoided by herbivores (wild rocket; Diplotaxis tenuifolia), and a small ruminant (sheep; Ovis aries) as models. Thirty-six sheep were randomly assigned to four treatments (n=9) where animals consumed: wild rocket ("DT"), wild rocket followed by a protein supplement ("DT+P"), wild rocket followed by a protein supplement+a mineral supplement containing iodine and copper ("DT+P+M"), or alfalfa pellets in amounts that paired the ingestion of wild rocket by DT ("CTRL"). Towards the end of the phase of exposure (day 35), DT showed the lowest intake of wild rocket, as well as reduced levels of plasma thyroid hormones (T3 and T4), alanine aminotransferase, and a trend towards reduced hemoglobin relative to DT+P and DT+P+M. Total concentration of serum proteins and albumins were greater in sheep fed the protein supplements, which have probably elicited a protective effect on toxin ingestion. Foraging behavior was then evaluated in an experimental arena where animals could select among randomly distributed buckets containing a fixed amount of wild rocket or variable amounts of barley grain (a preferred food). Regardless of barley grain availability, DT showed lower intake and lower times spent eating wild rocket than DT+P and DT+P+M. Unexpectedly, CTRL (without previous experience with wild rocket) ingested amounts of wild rocket comparable to those observed by DT+P and DT+P+M. A negative feeding experience with wild rocket is needed for animals to display the typical pattern of aversion commonly observed in grazing conditions.


Assuntos
Tomada de Decisões/fisiologia , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Preferências Alimentares , Plantas Tóxicas/efeitos adversos , Ovinos/fisiologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Antiparasitários/farmacologia , Aspartato Aminotransferases/sangue , Tomada de Decisões/efeitos dos fármacos , Glucosinolatos/toxicidade , Ivermectina/farmacologia
12.
Addict Biol ; 21(4): 885-94, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-25818161

RESUMO

A major problem in the treatment of addiction is predicting and preventing relapse following a rehabilitation program. Recently, in preclinical rodent studies dehydroepiandrosterone (DHEA) was found to markedly improve the resistance to drug reuse. In a double-blind, placebo-controlled study, we examined the effect of DHEA on relapse rates in adult polydrug users taking part in a detoxification program enriched with intensive psychosocial interventions and aftercare. During treatment, participants (79 percent males, mean age 28) consumed DHEA (100 mg/day) or placebo daily for at least 30 days. Of the 121 initial volunteers, 64 participated for at least 1 month. While in treatment, DHEA reduced negative affect on the Positive and Negative Affect Scale (F = 4.25, P = 0.04). Furthermore, in a 16-month follow-up, we found that reuse rates in the DHEA condition were about a third compared with placebo (12 versus 38 percent; χ(2) = 5.03, P = 0.02). DHEA treatment also resulted in an increase in DHEA sulfate (DHEA-S) 1 month following treatment, and the level of DHEA-S predicted relapse in the follow-up assessment.


Assuntos
Afeto/efeitos dos fármacos , Tomada de Decisões/efeitos dos fármacos , Desidroepiandrosterona/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Israel , Masculino , Recidiva , Transtornos Relacionados ao Uso de Substâncias/psicologia , Resultado do Tratamento , Adulto Jovem
13.
Hum Brain Mapp ; 35(7): 2935-49, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24142410

RESUMO

Sedation has a graded effect on brain responses to auditory stimuli: perceptual processing persists at sedation levels that attenuate more complex processing. We used fMRI in healthy volunteers sedated with propofol to assess changes in neural responses to spoken stimuli. Volunteers were scanned awake, sedated, and during recovery, while making perceptual or semantic decisions about nonspeech sounds or spoken words respectively. Sedation caused increased error rates and response times, and differentially affected responses to words in the left inferior frontal gyrus (LIFG) and the left inferior temporal gyrus (LITG). Activity in LIFG regions putatively associated with semantic processing, was significantly reduced by sedation despite sedated volunteers continuing to make accurate semantic decisions. Instead, LITG activity was preserved for words greater than nonspeech sounds and may therefore be associated with persistent semantic processing during the deepest levels of sedation. These results suggest functionally distinct contributions of frontal and temporal regions to semantic decision making. These results have implications for functional imaging studies of language, for understanding mechanisms of impaired speech comprehension in postoperative patients with residual levels of anesthetic, and may contribute to the development of frameworks against which EEG based monitors could be calibrated to detect awareness under anesthesia.


Assuntos
Mapeamento Encefálico , Encéfalo/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Propofol/farmacologia , Semântica , Estimulação Acústica , Adulto , Análise de Variância , Encéfalo/irrigação sanguínea , Tomada de Decisões/efeitos dos fármacos , Feminino , Humanos , Hipnóticos e Sedativos/sangue , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Propofol/sangue , Tempo de Reação/efeitos dos fármacos , Estatística como Assunto , Vocabulário , Adulto Jovem
14.
J Neurophysiol ; 106(2): 960-73, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21613584

RESUMO

Cognitive flexibility depends on the integrity of the prefrontal cortex (PFC). We showed previously that impaired decision making in pain results from amygdala-driven inhibition of medial PFC neurons, but the underlying mechanisms remain to be determined. Using whole cell patch clamp in rat brain slices and a cognitive behavioral task, we tested the hypothesis that group I metabotropic glutamate receptors (mGluRs) activate feed-forward inhibition to decrease excitability and output function of PFC pyramidal cells, thus impairing decision making. Polysynaptic inhibitory postsynaptic currents (IPSCs) and monosynaptic excitatory postsynaptic currents (EPSCs) were evoked in layer V pyramidal cells by stimulating presumed amygdala afferents. An mGluR1/5 agonist [(S)-3,5-dihydroxyphenylglycine, DHPG] increased synaptic inhibition more strongly than excitatory transmission. The facilitatory effects were blocked by an mGluR1 [(S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid, LY367385], but not mGluR5, antagonist, 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine. IPSCs were blocked by bicuculline and decreased by 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt (NBQX). Facilitation of synaptic inhibition by DHPG was glutamate driven because it was blocked by NBQX. DHPG increased frequency but not amplitude of spontaneous IPSCs; consistent with action potential-dependent synaptic inhibition, tetrodotoxin (TTX) prevented the facilitatory effects. DHPG decreased synaptically evoked spikes (E-S coupling) and depolarization-induced spiking [frequency-current (f-I) relationship]. This effect was indirect, resulting from glutamate-driven synaptic inhibition, because it persisted when a G protein blocker was included in the pipette but was blocked by GABA(A) receptor antagonists and NBQX. In contrast, DHPG increased E-S coupling and f-I relationships in mPFC interneurons through a presynaptic action, further supporting the concept of feed-forward inhibition. DHPG also impaired the ability of the animals to switch strategies in a decision-making task; bicuculline restored normal decision making, whereas a GABA(A) receptor agonist (muscimol) mimicked the decision-making deficit. The results show that mGluR1 activates feed-forward inhibition of PFC pyramidal cells to impair cognitive functions.


Assuntos
Tomada de Decisões/fisiologia , Inibição Neural/fisiologia , Córtex Pré-Frontal/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia , Animais , Biorretroalimentação Psicológica , Tomada de Decisões/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Potenciais Pós-Sinápticos Inibidores/fisiologia , Masculino , Metoxi-Hidroxifenilglicol/análogos & derivados , Metoxi-Hidroxifenilglicol/farmacologia , Inibição Neural/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Córtex Pré-Frontal/efeitos dos fármacos , Quinoxalinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor de Glutamato Metabotrópico 5 , Receptores de Glutamato Metabotrópico/antagonistas & inibidores
15.
J Vis Exp ; (49)2011 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-21403636

RESUMO

Behavioral endocrinological research in humans as well as in animals suggests that testosterone plays a key role in social interactions. Studies in rodents have shown a direct link between testosterone and aggressive behavior(1) and folk wisdom adapts these findings to humans, suggesting that testosterone induces antisocial, egoistic or even aggressive behavior(2). However, many researchers doubt a direct testosterone-aggression link in humans, arguing instead that testosterone is primarily involved in status-related behavior(3,4). As a high status can also be achieved by aggressive and antisocial means it can be difficult to distinguish between anti-social and status seeking behavior. We therefore set up an experimental environment, in which status can only be achieved by prosocial means. In a double-blind and placebo-controlled experiment, we administered a single sublingual dose of 0.5 mg of testosterone (with a hydroxypropyl-ß-cyclodextrin carrier) to 121 women and investigated their social interaction behavior in an economic bargaining paradigm. Real monetary incentives are at stake in this paradigm; every player A receives a certain amount of money and has to make an offer to another player B on how to share the money. If B accepts, she gets what was offered and player A keeps the rest. If B refuses the offer, nobody gets anything. A status seeking player A is expected to avoid being rejected by behaving in a prosocial way, i.e. by making higher offers. The results show that if expectations about the hormone are controlled for, testosterone administration leads to a significant increase in fair bargaining offers compared to placebo. The role of expectations is reflected in the fact that subjects who report that they believe to have received testosterone make lower offers than those who say they believe that they were treated with a placebo. These findings suggest that the experimental economics approach is sensitive for detecting neurobiological effects as subtle as those achieved by administration of hormones. Moreover, the findings point towards the importance of both psychosocial as well as neuroendocrine factors in determining the influence of testosterone on human social behavior.


Assuntos
Comportamento/efeitos dos fármacos , Tomada de Decisões/efeitos dos fármacos , Testosterona/administração & dosagem , Comportamento/fisiologia , Tomada de Decisões/fisiologia , Método Duplo-Cego , Economia , Endocrinologia/métodos , Feminino , Humanos , Testosterona/fisiologia
16.
Drug Alcohol Depend ; 112(3): 220-5, 2010 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-20729009

RESUMO

Cognitive deficits that are reported in heavy marijuana users (attention, memory, affect perception, decision-making) appear to be completely reversible after a prolonged abstinence period of about 28 days. However, it remains unclear whether the reversibility of these cognitive deficits indicates that (1) chronic marijuana use is not associated with long-lasting changes in cortical networks or (2) that such changes occur but the brain adapts to and compensates for the drug-induced changes. Therefore, we examined whether chronic marijuana smokers would demonstrate a differential pattern of response in comparison to healthy volunteers on a decision-making paradigm (Risk Task) while undergoing sham or active transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). Twenty-five chronic marijuana users who were abstinent for at least 24h were randomly assigned to receive left anodal/right cathodal tDCS of DLPFC (n=8), right anodal/left cathodal tDCS of DLPFC (n=9), or sham stimulation (n=8); results on Risk Task during sham/active tDCS were compared to healthy volunteers from a previously published dataset. Chronic marijuana users demonstrated more conservative (i.e. less risky) decision-making during sham stimulation. While right anodal stimulation of the DLPFC enhanced conservative decision-making in healthy volunteers, both right anodal and left anodal DLPFC stimulation increased the propensity for risk-taking in marijuana users. These findings reveal alterations in the decision-making neural networks among chronic marijuana users. Finally, we also assessed the effects of tDCS on marijuana craving and observed that right anodal/left cathodal tDCS of DLPFC is significantly associated with a diminished craving for marijuana.


Assuntos
Terapia por Estimulação Elétrica , Fumar Maconha/psicologia , Córtex Pré-Frontal/fisiologia , Assunção de Riscos , Atenção/efeitos dos fármacos , Atenção/fisiologia , Cannabis , Tomada de Decisões/efeitos dos fármacos , Tomada de Decisões/fisiologia , Método Duplo-Cego , Terapia por Estimulação Elétrica/efeitos adversos , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Risco
17.
Hum Psychopharmacol ; 25(6): 491-9, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20737522

RESUMO

OBJECTIVE: Although the serotonin precursor 5-hydroxytryptophan (5-HTP) is marketed as a psychoactive nutritional supplement, knowledge is limited regarding the effects of exogenous 5-HTP on brain activity. This study examined if oral administration of 5-HTP to healthy adults impacted: (1) mood states, as measured by the Profile of Mood States (POMS); and (2) performance on the Iowa Gambling Task (IGT), a measure sensitive to alterations in frontocortical serotonin levels. METHODS: A sample of 46 undergraduates participated, and each received either two 50 mg 5-HTP capsules or placebos, and completed the IGT and POMS following an absorption period. RESULTS: 5-HTP did not significantly alter mood states, but did impair performance on the IGT. Specifically, the 5-HTP group performed more poorly than the placebo group during the first 20 trials of the IGT but did not differ from the placebo group on trials 21-100. This suggests that oral 5-HTP specifically impaired decision making under ambiguity but not under risk. Males also performed more poorly on the first 20 trials of the IGT, regardless of treatment group. CONCLUSIONS: Oral 5-HTP is psychoactive at low doses. Decisions made under ambiguity may be differentially sensitive to increased serotonin release or associated reductions in frontocortical dopamine activity.


Assuntos
5-Hidroxitriptofano/farmacologia , Tomada de Decisões/efeitos dos fármacos , Jogo de Azar/psicologia , Psicotrópicos/farmacologia , 5-Hidroxitriptofano/administração & dosagem , Administração Oral , Afeto/efeitos dos fármacos , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Julgamento , Masculino , Testes Neuropsicológicos , Resolução de Problemas , Psicotrópicos/administração & dosagem , Risco , Fatores Sexuais , Estudantes , Adulto Jovem
18.
Brain Cogn ; 71(3): 354-61, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19679384

RESUMO

This fMRI study examined the neural correlates of the observed improvement in advantageous risk-taking behavior, as measured by the number of adjusted pumps in the Balloon Analogue Risk Task (BART), following a 60-day course of a Traditional Chinese Medicine (TCM) recipe, specifically designed to regulate impulsiveness in order to modulate risk-taking behavior. The 14 participants recruited for this study were randomly assigned to the experimental and control groups and the TCM recipe (Panax, 520 mg; Astragalus membranaceous Bunge, 520 mg; Masnetitum, 840 mg; Ostrea gigas Thumb, 470 mg; Thinleaf Milkwort Root Radix Polygalae, 450 mg; and Os Draconis, 470 mg) was administered, as a diet supplement, to the seven participants in the experimental group. The neural activity of the two groups was monitored by a 3T MRI scanner, before and after the 60-day treatment. Associated with the improved advantageous risk-taking behavior seen in the experimental group, significantly stronger blood oxygenation level dependent (BOLD) responses were observed in the bilateral dorsolateral prefrontal cortex (DLPFC), left putamen, left thalamus, right insula, and right anterior cingulate cortex (ACC), regions which have previously been reported as being involved in risk-taking decision making. The effect of the TCM in improving advantageous risk-taking decision making appears to have been related to the enhanced efficiency of the cognitive affective system, the PFC-ACC-insula-striatum network, which functions to inhibit impulsiveness, to sensitize reward-related information, and to allow the opportunity, during risk estimation, to evaluate potential gains and losses. The findings of this study suggest that interventions acting on factors modulating risk-taking decision making could have a beneficial effect in terms of optimizing risk-taking behavior.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Tomada de Decisões/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Assunção de Riscos , Adulto , Afeto/efeitos dos fármacos , Afeto/fisiologia , Mapeamento Encefálico , Tomada de Decisões/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Comportamento Impulsivo , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos
19.
J Psychopharmacol ; 23(7): 831-40, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18583436

RESUMO

Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation may be beneficial in the treatment of several psychiatric disorders, including depression. A small number of studies have suggested that there may also be cognitive and mood effects in healthy samples. The purpose of the present study was to investigate the effects of n-3 PUFA on depression-relevant cognitive functioning in healthy individuals. Fifty-four healthy university students were randomized to receive either n-3 PUFA supplements or placebo for 4 weeks in a double-blind design. The test battery included measures of cognitive reactivity, attention, response inhibition, facial emotion recognition, memory and risky decision-making. Results showed few effects of n-3 PUFAs on cognition and mood states. The n-3 PUFA group made fewer risk-averse decisions than the placebo group. This difference appeared only in non-normative trials of the decision-making test, and was not accompanied by increased impulsiveness. N-3 PUFAs improved scores on the control/perfectionism scale of the cognitive reactivity measure. No effects were found on the other cognitive tasks and no consistent effects on mood were observed. The present findings indicate that n-3 PUFA supplementation may have a selective effect on risky decision making in healthy volunteers, which is unrelated to impulsiveness.


Assuntos
Cognição/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Afeto/efeitos dos fármacos , Tomada de Decisões/efeitos dos fármacos , Depressão/dietoterapia , Suplementos Nutricionais , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/uso terapêutico , Feminino , Humanos , Masculino , Cooperação do Paciente , Desempenho Psicomotor/efeitos dos fármacos , Adulto Jovem
20.
Psychopharmacology (Berl) ; 179(4): 761-8, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15696331

RESUMO

RATIONALE: We have previously shown that a 60-g mixture of branched chain amino acids (BCAAs) lowers the plasma availability of the catecholamine precursors tyrosine (TYR) and phenylalanine (PHE) and produces biochemical and neuropsychological changes consistent with impaired dopamine neurotransmission. However, the BCAA mixture also lowers the ratio of tryptophan (TRP) to BCAA which could impair brain serotonin function. OBJECTIVES: To determine the biochemical and neuropsychological effects of a BCAA mixture supplemented with TRP. METHODS: We studied 32 healthy volunteers who were randomly and blindly allocated to either a single administration of amino acid mixture (60 g BCAA and 2 g TRP) or placebo. We carried out venous sampling to measure plasma levels of amino acids and performed selected cognitive tasks sensitive to monoamine manipulation 5 h after mixture ingestion. RESULTS: Relative to placebo, the BCAA/TRP mixture substantially lowered the ratio of TYR+PHE:BCAA and increased plasma prolactin. The ratio of TRP:BCAA was also lowered but to a lesser extent. The BCAA/TRP mixture produced significant changes in a task of decision-making where volunteers showed reduced discrimination between gambles with large and small losses. CONCLUSIONS: A 62 g BCAA/TRP mixture decreases the availability of TYR and PHE for brain catecholamine synthesis and increases plasma prolactin consistent with lowered brain dopamine function. Addition of 2 g TRP to the 60 g BCAA mixture does not prevent a reduction of the ratio TRP:BCAA relative to placebo. The effects of the BCAA/TRP mixture on decision-making suggest a general action of dopamine pathways on the processing of emotional information in risky choice, including punishment-related cues, consistent with suggestions that dopamine mechanisms mediate behavioural responses to aversive as well as appetitive stimuli in instrumental conditioning.


Assuntos
Aminoácidos de Cadeia Ramificada/farmacologia , Tomada de Decisões/efeitos dos fármacos , Neurotransmissores/fisiologia , Triptofano/farmacologia , Adulto , Afeto/efeitos dos fármacos , Idoso , Química Encefálica/efeitos dos fármacos , Sinais (Psicologia) , Método Duplo-Cego , Feminino , Jogo de Azar/psicologia , Humanos , Masculino , Memória/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Reconhecimento Visual de Modelos/efeitos dos fármacos , Fenilalanina/metabolismo , Prolactina/sangue , Desempenho Psicomotor/efeitos dos fármacos , Percepção Espacial/efeitos dos fármacos
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