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1.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802338

RESUMO

Early life stress (ELS) is strongly associated with psychiatric disorders such as anxiety, depression, and schizophrenia in adulthood. To date, biological, behavioral, and structural aspects of ELS have been studied extensively, but their functional effects remain unclear. Here, we examined NeuroPET studies of dopaminergic, glutamatergic, and serotonergic systems in ELS animal models. Maternal separation and restraint stress were used to generate single or complex developmental trauma. Body weights of animals exposed to single trauma were similar to those of control animals; however, animals exposed to complex trauma exhibited loss of body weight when compared to controls. In behavioral tests, the complex developmental trauma group exhibited a decrease in time spent in the open arm of the elevated plus-maze and an increase in immobility time in the forced swim test when compared to control animals. In NeuroPET studies, the complex trauma group displayed a reduction in brain uptake values when compared to single trauma and control groups. Of neurotransmitter systems analyzed, the rate of decrease in brain uptake was the highest in the serotonergic group. Collectively, our results indicate that developmental trauma events induce behavioral deficits, including anxiety- and depressive-like phenotypes and dysfunction in neurotransmitter systems.


Assuntos
Encéfalo/metabolismo , Encéfalo/fisiologia , Neurotransmissores/metabolismo , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/fisiopatologia , Animais , Animais Recém-Nascidos/metabolismo , Animais Recém-Nascidos/fisiologia , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Transtornos de Ansiedade/metabolismo , Transtornos de Ansiedade/fisiopatologia , Comportamento Animal/fisiologia , Depressão/metabolismo , Depressão/fisiopatologia , Modelos Animais de Doenças , Comportamento Exploratório/fisiologia , Feminino , Masculino , Privação Materna , Aprendizagem em Labirinto/fisiologia , Imagem Molecular/métodos , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Natação/fisiologia
2.
Neurosci Lett ; 745: 135617, 2021 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-33421492

RESUMO

Hepatic encephalopathy (HE) is a cerebral function alteration in patients with liver dysfunction. The present study aimed to evaluate the therapeutic effects of thymoquinone (TQ) on behavioral deficits and its possible mechanism(s) in a thioacetamide (TAA)-induced HE model. HE was induced in male Wistar rats by intraperitoneal (i.p.) injection of TAA (200 mg/kg) for once every 48 h for 14 consecutive days. Thymoquinone (5, 10, and 20 mg/kg) was administered for seven consecutive days (i.p.) after HE induction. Anxiety and depression-like behaviors assessed by standard paradigms respectively. Finally, their brain hippocampus sections prepared to evaluate the oxidative stress changes in rats. Data showed treatment HE rats with TQ ameliorated anxiety and depression-like behaviors. TQ administration also reduced oxidative stress due to its potential to enhance the levels of glutathione-peroxidase (GPx), catalase (CAT), and total thiol content in the hippocampus. These findings suggest that TQ has notable effects against acute hepatic failure and HE complications through modulation of oxidative stress.


Assuntos
Benzoquinonas/uso terapêutico , Encefalopatia Hepática/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Tioacetamida/toxicidade , Animais , Benzoquinonas/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Encefalopatia Hepática/induzido quimicamente , Encefalopatia Hepática/metabolismo , Hipocampo/química , Hipocampo/metabolismo , Locomoção/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Wistar
3.
PLoS Biol ; 18(9): e3000828, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32936797

RESUMO

Many herbivorous insects are mono- or oligophagous, having evolved to select a limited range of host plants. They specifically identify host-plant leaves using their keen sense of taste. Plant secondary metabolites and sugars are thought to be key chemical cues that enable insects to identify host plants and evaluate their quality as food. However, the neuronal and behavioral mechanisms of host-plant recognition are poorly understood. Here, we report a two-factor host acceptance system in larvae of the silkworm Bombyx mori, a specialist on several mulberry species. The first step is controlled by a chemosensory organ, the maxillary palp (MP). During palpation at the leaf edge, the MP detects trace amounts of leaf-surface compounds, which enables host-plant recognition without biting. Chemosensory neurons in the MP are tuned with ultrahigh sensitivity (thresholds of attomolar to femtomolar) to chlorogenic acid (CGA), quercetin glycosides, and ß-sitosterol (ßsito). Only if these 3 compounds are detected does the larva make a test bite, which is evaluated in the second step. Low-sensitivity neurons in another chemosensory organ, the maxillary galea (MG), mainly detect sucrose in the leaf sap exuded by test biting, allowing larvae to accept the leaf and proceed to persistent biting (feeding). The two-factor host acceptance system reported here may commonly underlie stereotyped feeding behavior in many phytophagous insects and determine their feeding habits.


Assuntos
Bombyx/fisiologia , Comportamento de Escolha , Dieta , Comportamento Alimentar/fisiologia , Larva/fisiologia , Papilas Gustativas/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Comportamento Animal/fisiologia , Bombyx/anatomia & histologia , Bombyx/crescimento & desenvolvimento , Células Quimiorreceptoras/fisiologia , Quimiotaxia/fisiologia , Sinais (Psicologia) , Comportamento Exploratório/fisiologia , Interações Hospedeiro-Parasita/fisiologia , Larva/anatomia & histologia , Larva/citologia , Morus/química , Folhas de Planta/química , Paladar/fisiologia , Papilas Gustativas/anatomia & histologia
4.
Science ; 369(6507)2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32855307

RESUMO

Everyday life often requires arbitrating between pursuing an ongoing action plan by possibly adjusting it versus exploring a new action plan instead. Resolving this so-called exploitation-exploration dilemma involves the medial prefrontal cortex (mPFC). Using human intracranial electrophysiological recordings, we discovered that neural activity in the ventral mPFC infers and tracks the reliability of the ongoing plan to proactively encode upcoming action outcomes as either learning signals or potential triggers to explore new plans. By contrast, the dorsal mPFC exhibits neural responses to action outcomes, which results in either improving or abandoning the ongoing plan. Thus, the mPFC resolves the exploitation-exploration dilemma through a two-stage, predictive coding process: a proactive ventromedial stage that constructs the functional signification of upcoming action outcomes and a reactive dorsomedial stage that guides behavior in response to action outcomes.


Assuntos
Comportamento Exploratório/fisiologia , Aprendizagem/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/citologia
5.
Proc Biol Sci ; 287(1928): 20200057, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32517624

RESUMO

Social interactions can influence the expression and underlying genetic basis of many traits. Yet, empirical investigations of indirect genetic effects (IGEs) and genotype-by-genotype epistasis-quantitative genetics parameters representing the role of genetic variation in a focal individual and its interacting partners in producing the observed trait values-are still scarce. While it is commonly observed that an individual's traits are influenced by the traits of interacting conspecifics, representing social plasticity, studying this social plasticity and its quantitative-genetic basis is notoriously challenging. These challenges are compounded when individuals interact in groups, rather than (simpler) dyads. Here, we investigate the genetic architecture of social plasticity for exploratory behaviour, one of the most intensively studied behaviours in recent decades. Using genotypes of Drosophila simulans, we measured genotypes both alone, and in social groups representing a mix of two genotypes. We found that females adjusted their exploratory behaviour based on the behaviour of others in the group, representing social plasticity. However, the direction of this plasticity depended on the identity of group members: focal individuals were more likely to emerge from a refuge if group members who were the same genotype as the focal remained inside for longer. By contrast, focal individuals were less likely to emerge from a refuge if partner-genotype group members remained inside for longer. Exploratory behaviour also depended on the identities of both genotypes that composed the group. Together, these findings demonstrate genotype-by-genotype epistasis for exploratory behaviour both within and among groups.


Assuntos
Drosophila simulans/genética , Comportamento Exploratório/fisiologia , Genótipo , Animais , Epistasia Genética , Relações Interpessoais , Fenótipo , Comportamento Social
6.
Psychopharmacology (Berl) ; 237(8): 2435-2449, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32506234

RESUMO

RATIONALE: Νeurosteroids, like dehydroepiandrosterone (DHEA), play an important role in neurodegeneration and neural protection, but they are metabolized in androgens, estrogens, or other active metabolites. A newly developed synthetic DHEA analog, BNN27 ((20R)-3ß,21-dihydroxy-17R,20-epoxy-5-pregnene), exerts neurotrophic and neuroprotective actions without estrogenic or androgenic effects. OBJECTIVES: This study aimed to investigate potential anxiolytic or antidepressant properties of BNN27. METHODS: Male and female adult Wistar rats were treated with BNN27 (10, 30, or 90 mg/kg, i.p.) and subjected to behavioral tests measuring locomotion, exploration, and "depressive-like" behavior (open field, light/dark box, hole-board, and forced swim tests). The hippocampus and prefrontal cortex were collected for glutamate and GABA measurements, and trunk blood was collected for gonadal hormone analysis. RESULTS: Acute high-dose BNN27 reduced locomotion and exploratory behavior in both sexes. Intermediate acute doses (30 mg/kg) of BNN27 reduced exploration and testosterone levels only in males, and enhanced progesterone levels in both sexes. Notably, with the present design, BNN27 had neither anxiolytic nor antidepressant effects and did not affect estrogen levels. Interestingly, acute administration of a low BNN27 dose (10 mg/kg) increased glutamate turnover, GABA, and glutamine levels in the hippocampus. The same dose also enhanced glutamate levels in the prefrontal cortex of males only. Sex differences were apparent in the basal levels of behavioral, hormonal, and neurochemical parameters, as expected. CONCLUSIONS: BNN27 affects locomotion, progesterone, and testosterone levels, as well as the glutamatergic and GABAergic systems of the hippocampus and prefrontal cortex in a sex-dependent way.


Assuntos
Desidroepiandrosterona/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Neuroesteroides/farmacologia , Caracteres Sexuais , Animais , Desidroepiandrosterona/química , Comportamento Exploratório/fisiologia , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Locomoção/fisiologia , Masculino , Neuroesteroides/química , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Wistar
7.
Nat Commun ; 11(1): 2371, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398675

RESUMO

Most real-world decisions involve a delicate balance between exploring unfamiliar alternatives and committing to the best known option. Previous work has shown that humans rely on different forms of uncertainty to negotiate this "explore-exploit" trade-off, yet the neural basis of the underlying computations remains unclear. Using fMRI (n = 31), we find that relative uncertainty is represented in right rostrolateral prefrontal cortex and drives directed exploration, while total uncertainty is represented in right dorsolateral prefrontal cortex and drives random exploration. The decision value signal combining relative and total uncertainty to compute choice is reflected in motor cortex activity. The variance of this signal scales with total uncertainty, consistent with a sampling mechanism for random exploration. Overall, these results are consistent with a hybrid computational architecture in which different uncertainty computations are performed separately and then combined by downstream decision circuits to compute choice.


Assuntos
Comportamento de Escolha/fisiologia , Comportamento Exploratório/fisiologia , Modelos Neurológicos , Córtex Pré-Frontal/fisiologia , Incerteza , Adolescente , Adulto , Análise de Variância , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Adulto Jovem
8.
Psychopharmacology (Berl) ; 237(7): 2043-2053, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32419116

RESUMO

RATIONALE: In rodents, acute haloperidol treatment induces psychomotor impairments known as catalepsy, which models akinesia in humans and is characterized as an animal model of acute Parkinsonism, whereas sub-chronic haloperidol reduces exploratory behavior, which resembles bradykinesia. Haloperidol-induced catalepsy in rats can be ameliorated by playback of 50-kHz ultrasonic vocalizations (USV), an emotionally and motivationally relevant appetitive auditory stimulus, representing an animal model of paradoxical kinesia. In a condition like PD where patients suffer from chronic motor impairments, it is paramount to assess the long-term symptom relief in an animal model of Parkinsonism. OBJECTIVES: We investigated whether 50-kHz USV playback ameliorates psychomotor deficits induced by haloperidol in a sub-chronic dosing regimen. METHODS: In phase 1, distance traveled and number of rearing behavior were assessed in an activity chamber in order to investigate whether sub-chronic haloperidol treatment induced psychomotor impairments. In phase 2, we investigated whether 50-kHz USV playback could overcome these impairments by assessing exploratory behaviors and approach behavior towards the sound source in the 50-kHz USV radial maze playback paradigm. RESULTS: Sub-chronic haloperidol treatment led to psychomotor deficits since the distance traveled and number of rearing behavior were reduced as compared to saline control group or baseline. These psychomotor impairments were ameliorated during playback of 50-kHz USV, with haloperidol treated rats showing a clear social approach behavior towards the sound source exclusively during playback. CONCLUSIONS: This study provides evidence that 50-kHz USV playback induces paradoxical kinesia in rats exhibiting motor deficits after sub-chronic haloperidol, as we previously showed after acute haloperidol treatment.


Assuntos
Estimulação Acústica/métodos , Haloperidol/toxicidade , Transtornos Psicomotores/induzido quimicamente , Transtornos Psicomotores/terapia , Terapia por Ultrassom/métodos , Vocalização Animal/fisiologia , Animais , Modelos Animais de Doenças , Antagonistas de Dopamina/toxicidade , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Masculino , Transtornos Psicomotores/psicologia , Ratos , Ratos Wistar
9.
Nat Neurosci ; 23(7): 800-804, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32424287

RESUMO

Experiential diversity promotes well-being in animal models. Here, using geolocation tracking, experience sampling and neuroimaging, we found that daily variability in physical location was associated with increased positive affect in humans. This effect was stronger for individuals who exhibited greater functional coupling of the hippocampus and striatum. These results link diversity in real-world daily experiences to fluctuations in positive affect and identify a hippocampal-striatal circuit associated with this bidirectional relationship.


Assuntos
Afeto/fisiologia , Corpo Estriado/fisiologia , Comportamento Exploratório/fisiologia , Hipocampo/fisiologia , Vias Neurais/fisiologia , Adolescente , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
10.
J Neurosci ; 40(24): 4739-4749, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32393533

RESUMO

High trait anxiety is associated with altered activity across emotion regulation circuitry and a higher risk of developing anxiety disorders and depression. This circuitry is extensively modulated by serotonin. Here, to understand why some people may be more vulnerable to developing affective disorders, we investigated whether serotonin-related gene expression across the brain's emotion regulation circuitry may underlie individual differences in trait anxiety using the common marmoset (Callithrix jacchus, mixed sexes) as a model. First, we assessed the association of region-specific expression of the serotonin transporter (SLC6A4) and serotonin receptor (HTR1A, HTR2A, HTR2C) genes with anxiety-like behavior; and second, we investigated their causal role in two key features of the high trait anxious phenotype: high responsivity to anxiety-provoking stimuli and an exaggerated conditioned threat response. While the expression of the serotonin receptors did not show a significant relationship with anxiety-like behavior in any of the targeted brain regions, serotonin transporter expression, specifically within the right ventrolateral prefrontal cortex (vlPFC) and most strongly in the right amygdala, was associated positively with anxiety-like behavior. The causal relationship between amygdala serotonin levels and an animal's sensitivity to threat was confirmed via direct amygdala infusions of a selective serotonin reuptake inhibitor (SSRI), citalopram. Both anxiety-like behaviors, and conditioned threat-induced responses were reduced by the blockade of serotonin reuptake in the amygdala. Together, these findings provide evidence that high amygdala serotonin transporter expression contributes to the high trait anxious phenotype and suggest that reduction of threat reactivity by SSRIs may be mediated by their actions in the amygdala.SIGNIFICANCE STATEMENT Findings here contribute to our understanding of how the serotonin system underlies an individual's expression of threat-elicited negative emotions such as anxiety and fear within nonhuman primates. Exploration of serotonergic gene expression across brain regions implicated in emotion regulation revealed that serotonin transporter gene expression in the ventrolateral prefrontal cortex (vlPFC) and most strongly in the amygdala, but none of the serotonin receptor genes, were predictive of interindividual differences in anxiety-like behavior. Targeting of amygdala serotonin reuptake with selective serotonin reuptake inhibitors (SSRIs) confirmed the causal relationship between amygdala serotonin transporter and an animal's sensitivity to threat by reversing expression of two key features of the high trait-like anxiety phenotype: high responsivity to anxiety-provoking uncertain threat and responsivity to certain conditioned threat.


Assuntos
Tonsila do Cerebelo/metabolismo , Ansiedade/metabolismo , Emoções/fisiologia , Comportamento Exploratório/fisiologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Ansiedade/genética , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Callithrix , Citalopram/farmacologia , Emoções/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Extinção Psicológica/fisiologia , Medo/efeitos dos fármacos , Medo/fisiologia , Feminino , Humanos , Masculino , Receptores de Serotonina/genética , Receptores de Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Inibidores de Captação de Serotonina/farmacologia
11.
PLoS One ; 15(5): e0232492, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413032

RESUMO

Coyotes (Canis latrans) and kit foxes (Vulpes macrotis) are desert canids that share ecological similarities, but have disparate histories with anthropogenic pressure that may influence their responses towards novel stimuli. We used remote cameras to investigate response to novel stimuli for these two species. We predicted that coyotes (heavily pressured species) would be more wary towards novel stimuli on unprotected land (canid harvest activities are permitted) than in protected areas (canid harvest activities are not permitted), whereas kit foxes (less pressured species) would exhibit no difference. We examined differences in the investigative behaviors at 660 scent stations in both protected and unprotected areas. Coyotes showed no differences between protected and unprotected land and were generally more wary than kit foxes, supporting our prediction. Kit foxes were more investigative on protected land, contrary to our expectations. Our study provides evidence that anthropogenic pressure can alter the behaviors of wildlife species.


Assuntos
Comportamento Animal/fisiologia , Coiotes/fisiologia , Raposas/fisiologia , Animais , Animais Selvagens/fisiologia , Clima Desértico , Espécies em Perigo de Extinção , Comportamento Exploratório/fisiologia , Odorantes , Feromônios/fisiologia , Fotografação , Tecnologia de Sensoriamento Remoto , Especificidade da Espécie , Utah
12.
PLoS Biol ; 18(5): e3000571, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32453721

RESUMO

Animals actively move their sensory organs in order to acquire sensory information. Some rodents, such as mice and rats, employ cyclic scanning motions of their facial whiskers to explore their proximal surrounding, a behavior known as whisking. Here, we investigated the contingency of whisking kinematics on the animal's behavioral context that arises from both internal processes (attention and expectations) and external constraints (available sensory and motor degrees of freedom). We recorded rat whisking at high temporal resolution in 2 experimental contexts-freely moving or head-fixed-and 2 spatial sensory configurations-a single row or 3 caudal whiskers on each side of the snout. We found that rapid sensorimotor twitches, called pumps, occurring during free-air whisking carry information about the rat's upcoming exploratory direction, as demonstrated by the ability of these pumps to predict consequent head and body locomotion. Specifically, pump behavior during both voluntary motionlessness and imposed head fixation exposed a backward redistribution of sensorimotor exploratory resources. Further, head-fixed rats employed a wide range of whisking profiles to compensate for the loss of head- and body-motor degrees of freedom. Finally, changing the number of intact vibrissae available to a rat resulted in an alteration of whisking strategy consistent with the rat actively reallocating its remaining resources. In sum, this work shows that rats adapt their active exploratory behavior in a homeostatic attempt to preserve sensorimotor coverage under changing environmental conditions and changing sensory capacities, including those imposed by various laboratory conditions.


Assuntos
Adaptação Fisiológica , Comportamento Exploratório/fisiologia , Retroalimentação Sensorial , Movimentos da Cabeça , Vibrissas/fisiologia , Animais , Fenômenos Biomecânicos , Locomoção , Masculino , Ratos Wistar
13.
J Youth Adolesc ; 49(6): 1162-1178, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32335842

RESUMO

Positive risks benefit adolescent development without posing the same public safety concerns as negative risks, but little is understood about the psychological characteristics of positive risk taking. This study explored the shared and unique correlates of positive and negative risk taking in 223 adolescents (48% female) ages 16-20 years (M = 18.1; SD = 0.81). Positive and negative risk taking were both associated with higher sensation seeking. Unlike negative risk taking, positive risk taking was not associated with impulsivity or risk taking on experimental tasks. Further, positive risk taking was associated with lower reward sensitivity, higher punishment sensitivity, and greater school engagement than negative risk taking. The findings offer new insights for prevailing models of adolescent risk behavior and suggest positive risk taking may be particularly beneficial in the school context.


Assuntos
Comportamento do Adolescente/psicologia , Comportamento Exploratório/fisiologia , Comportamento Impulsivo , Controle Interno-Externo , Assunção de Riscos , Adolescente , Desenvolvimento do Adolescente , Fatores Etários , Feminino , Humanos , Masculino , Punição , Recompensa , Adulto Jovem
14.
PLoS One ; 15(4): e0230900, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240211

RESUMO

Reliability of data has become a major concern in the course of the reproducibility crisis. Especially when studying animal behavior, confounding factors such as novelty of the test apparatus can lead to a wide variability of data which may mask treatment effects and consequently lead to misinterpretation. Habituation to the test situation is a common practice to circumvent novelty induced increases in variance and to improve the reliability of the respective measurements. However, there is a lack of published empirical knowledge regarding reasonable habituation procedures and a method validation seems to be overdue. This study aimed at setting up a simple strategy to increase reliability of behavioral data measured in a familiar test apparatus. Therefore, exemplary data from mice tested in an Open Field (OF) arena were used to elucidate the potential of habituation and how reliability of measures can be confirmed by means of a repeatability analysis using the software R. On seven consecutive days, male C57BL/6J, BALB/cJ and 129S1/SvImJ mice were tested in an OF arena once daily and individual mouse behavior was recorded. A repeatability analysis was conducted with regard to repeated trials of habituation. Our data analysis revealed that monitoring animal behavior during habituation is important to determine when individual differences of the measurements are stable. Repeatability values from distance travelled and average activity increased over the habituation period, revealing that around 60% of the variance of the data can be explained by individual differences between mice. The first day of habituation was significantly different from the following 6 days. A three-day habituation period appeared to be sufficient in this study. Overall, these results emphasize the importance of habituation and in depth analysis of habituation data to define the correct starting point of the experiment for improving the reliability and reproducibility of experimental data.


Assuntos
Comportamento Animal/fisiologia , Comportamento Exploratório/fisiologia , Habituação Psicofisiológica/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Atividade Motora/fisiologia , Reprodutibilidade dos Testes , Especificidade da Espécie
15.
Nat Hum Behav ; 4(5): 531-543, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32231281

RESUMO

Curiosity is often portrayed as a desirable feature of human faculty. However, curiosity may come at a cost that sometimes puts people in harmful situations. Here, using a set of behavioural and neuroimaging experiments with stimuli that strongly trigger curiosity (for example, magic tricks), we examine the psychological and neural mechanisms underlying the motivational effect of curiosity. We consistently demonstrate that across different samples, people are indeed willing to gamble, subjecting themselves to electric shocks to satisfy their curiosity for trivial knowledge that carries no apparent instrumental value. Also, this influence of curiosity shares common neural mechanisms with that of hunger for food. In particular, we show that acceptance (compared to rejection) of curiosity-driven or incentive-driven gambles is accompanied by enhanced activity in the ventral striatum when curiosity or hunger was elicited, which extends into the dorsal striatum when participants made a decision.


Assuntos
Corpo Estriado/fisiologia , Tomada de Decisões/fisiologia , Comportamento Exploratório , Fome/fisiologia , Estriado Ventral/diagnóstico por imagem , Estriado Ventral/fisiologia , Corpo Estriado/diagnóstico por imagem , Eletrochoque/psicologia , Comportamento Exploratório/fisiologia , Feminino , Jogo de Azar/diagnóstico por imagem , Jogo de Azar/fisiopatologia , Humanos , Magia/psicologia , Imagem por Ressonância Magnética , Masculino , Motivação/fisiologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Neuroimagem , Núcleo Accumbens/diagnóstico por imagem , Núcleo Accumbens/fisiologia , Adulto Jovem
17.
Sci Rep ; 10(1): 4002, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152383

RESUMO

The retrosplenial cortex (RSC) is implicated on navigation and contextual memory. Lesions studies showed that the RSC shares functional similarities with the hippocampus (HP). Here we evaluated the role of the anterior RSC (aRSC) in the "what" and "where" components of recognition memory and contrasted it with that of the dorsal HP (dHP). Our behavioral and molecular findings show functional differences between the aRSC and the dHP in recognition memory. The inactivation of the aRSC, but not the dHP, impairs the consolidation and expression of the "what" memory component. In addition, object recognition task is accompanied by c-Fos levels increase in the aRSC. Interestingly, we found that the aRSC is recruited to process the "what" memory component only if it is active during acquisition. In contrast, both the aRSC and dHP are required for encoding the "where" component, which correlates with c-Fos levels increase. Our findings introduce a novel role of the aRSC in recognition memory, processing not only the "where", but also the "what" memory component.


Assuntos
Córtex Cerebral/fisiologia , Comportamento Exploratório/fisiologia , Memória de Longo Prazo/fisiologia , Reconhecimento Psicológico/fisiologia , Percepção Visual/fisiologia , Animais , Aprendizagem da Esquiva , Giro do Cíngulo/fisiologia , Hipocampo/fisiologia , Masculino , Ratos , Ratos Wistar
18.
Sci Rep ; 10(1): 4156, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139739

RESUMO

In order to maintain the energy balance, animals often exhibit several physiological adjustments when subjected to a decrease in resource availability. Specifically, some rodents show increases in behavioral activity in response to food restriction; a response regarded as a paradox because it would imply an investment in locomotor activity, despite the lack of trophic resources. Here, we aim to explore the possible existence of trade-offs between metabolic variables and behavioral responses when rodents are faced to stochastic deprivation of food and caloric restriction. Adult BALB/c mice were acclimatized for four weeks to four food treatments: two caloric regimens (ad libitum and 60% restriction) and two periodicities (continuous and stochastic). In these mice, we analyzed: exploratory behavior and home-cage behavior, basal metabolic rate, citrate synthase and cytochrome oxidase c enzyme activity (in liver and skeletal muscle), body temperature and non-shivering thermogenesis. Our results support the model of allocation, which indicates commitments between metabolic rates and exploratory behavior, in a caloric restricted environment. Specifically, we identify the role of thermogenesis as a pivotal budget item, modulating the reallocation of energy between behavior and basal metabolic rate. We conclude that brown adipose tissue and liver play a key role in the development of paradoxical responses when facing decreased dietary availability.


Assuntos
Comportamento Exploratório/fisiologia , Animais , Temperatura Corporal , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
19.
Psychopharmacology (Berl) ; 237(6): 1577-1593, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32076746

RESUMO

RATIONALE: Schizophrenia is a mental illness which is characterised by positive and negative symptoms and by cognitive impairments. While the major prevailing hypothesis is that altered dopaminergic and/or glutamatergic transmission contributes to this disease, there is evidence that the noradrenergic system also plays a role in its major symptoms. OBJECTIVES: In the present paper, we investigated the pro-cognitive effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) an endogenous neuroprotective compound, on ketamine-modelled schizophrenia in rats. METHODS: We used an antagonist of NMDA receptors (ketamine) to model memory deficit symptoms in rats. Using the novel object recognition (NOR) test, we investigated the pro-cognitive effect of 1MeTIQ. Additionally, olanzapine, an atypical antipsychotic drug, was used as a standard to compare the pro-cognitive effects of the substances. In vivo microdialysis studies allowed us to verify the changes in the release of monoamines and their metabolites in the rat striatum. RESULTS: Our study demonstrated that 1MeTIQ, similarly to olanzapine, exhibits a pro-cognitive effect in NOR test and enhances memory disturbed by ketamine treatment. Additionally, in vivo microdialysis studies have shown that ketamine powerfully increased noradrenaline release in the rat striatum, while 1MeTIQ and olanzapine completely antagonised this neurochemical effect. CONCLUSIONS: 1MeTIQ, as a possible pro-cognitive drug, in contrast to olanzapine, expresses beneficial neuroprotective activity in the brain, increasing concentration of the extraneuronal dopamine metabolite, 3-methoxytyramine (3-MT), which plays an important physiological role in the brain as an inhibitory regulator of catecholaminergic activity. Moreover, we first demonstrated the essential role of noradrenaline release in memory disturbances observed in the ketamine-model of schizophrenia, and its possible participation in negative symptoms of the schizophrenia.


Assuntos
Ketamina/toxicidade , Atividade Motora/efeitos dos fármacos , Nootrópicos/uso terapêutico , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Tetra-Hidroisoquinolinas/uso terapêutico , Animais , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Corpo Estriado/efeitos dos fármacos , Dopamina/análogos & derivados , Dopamina/metabolismo , Antagonistas de Aminoácidos Excitatórios/toxicidade , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Masculino , Microdiálise , Atividade Motora/fisiologia , Nootrópicos/farmacologia , Norepinefrina/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Reconhecimento Psicológico/efeitos dos fármacos , Reconhecimento Psicológico/fisiologia , Tetra-Hidroisoquinolinas/farmacologia , Resultado do Tratamento
20.
Psychopharmacology (Berl) ; 237(6): 1595-1606, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32088835

RESUMO

INTRODUCTION: Depression is characterized by behavioral, cognitive and physiological changes, imposing a major burden on the overall wellbeing of the patient. Some evidence indicates that social stress, changes in growth factors (e.g., brain-derived neurotrophic factor (BDNF)), and neuroinflammation are involved in the development and progression of the disease. The monoamine oxidase A inhibitor drug harmine was suggested to have both antidepressant and anti-inflammatory properties and may, therefore, be a potential candidate for treatment of depression. AIM: The goal of this study was to assess the effects of harmine on behavior, brain BDNF levels, and microglia activation in control rats and a rat model of social stress. MATERIAL AND METHODS: Rats were submitted to 5 consecutive days of repeated social defeat (RSD) or control conditions. Animals were treated daily with harmine (15 mg/kg) or vehicle from day 3 until the end of the experiment. To assess the effects of harmine treatment on behavior, the sucrose preference test (SPT) was performed on days 1, 6, and 15, the open field test (OFT) on days 6 and 14, and the novel object recognition test (NOR) on day 16. Brain microgliosis was assessed using [11C]PBR-28 PET on day 17. Animals were terminated on day 17, and BDNF protein concentrations in the hippocampus and frontal cortex were analyzed using ELISA. RESULTS: RSD significantly decreased bodyweight and increased anxiety and anhedonia-related parameters in the OFT and SPT on day 6, but these behavioral effects were not observed anymore on day 14/15. Harmine treatment caused a significant reduction in bodyweight gain in both groups, induced anhedonia in the SPT on day 6, and significantly reduced the mobility and exploratory behavior of the animals in the OFT mainly on day 14. PET imaging and the NOR test did not show any significant effects on microglia activation and memory, respectively. BDNF protein concentrations in the hippocampus and frontal cortex were not significantly affected by either RSD or harmine treatment. DISCUSSION: Harmine was not able to reverse the acute effects of RSD on anxiety and anhedonia and even aggravated the effect of RSD on bodyweight loss. Moreover, harmine treatment caused unexpected side effects on general locomotion, both in RSD and control animals, but did not influence glial activation status and BDNF concentrations in the brain. In this model, RSD-induced stress was not strong enough to induce long-term effects on the behavior, neuroinflammation, or BDNF protein concentration. Thus, the efficacy of harmine treatment on these delayed parameters needs to be further evaluated in more severe models of chronic stress.


Assuntos
Depressão/tratamento farmacológico , Depressão/metabolismo , Harmina/administração & dosagem , Inibidores da Monoaminoxidase/administração & dosagem , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Animais , Antidepressivos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/psicologia , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Ratos , Ratos Wistar , Estresse Psicológico/psicologia , Resultado do Tratamento
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