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2.
Lancet Psychiatry ; 8(4): 282-284, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33743881
3.
Lancet Oncol ; 21(11): 1412, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33152283
4.
BMC Evol Biol ; 20(1): 126, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962630

RESUMO

BACKGROUND: One hypothesis for the function of sleep is that it serves as a mechanism to conserve energy. Recent studies have suggested that increased sleep can be an adaptive mechanism to improve survival under food deprivation in Drosophila melanogaster. To test the generality of this hypothesis, we compared sleep and its plastic response to starvation in a temperate and tropical population of Drosophila melanogaster. RESULTS: We found that flies from the temperate population were more starvation resistant, and hypothesized that they would engage in behaviors that are considered to conserve energy, including increased sleep and reduced movement. Surprisingly, temperate flies slept less and moved more when they were awake compared to tropical flies, both under fed and starved conditions, therefore sleep did not correlate with population-level differences in starvation resistance. In contrast, total sleep and percent change in sleep when starved were strongly positively correlated with starvation resistance within the tropical population, but not within the temperate population. Thus, we observe unexpectedly complex relationships between starvation and sleep that vary both within and across populations. These observations falsify the simple hypothesis of a straightforward relationship between sleep and energy conservation. We also tested the hypothesis that starvation is correlated with metabolic phenotypes by investigating stored lipid and carbohydrate levels, and found that stored metabolites partially contributed towards variation starvation resistance. CONCLUSIONS: Our findings demonstrate that the function of sleep under starvation can rapidly evolve on short timescales and raise new questions about the physiological correlates of sleep and the extent to which variation in sleep is shaped by natural selection.


Assuntos
Drosophila melanogaster/genética , Evolução Molecular , Sono , Inanição , Animais , Teorema de Bayes , Drosophila melanogaster/fisiologia , Feminino , Masculino , Fenótipo
5.
Lancet Gastroenterol Hepatol ; 5(5): 439-440, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32277900
6.
Pain ; 157(12): 2697-2708, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27657698

RESUMO

The rostral ventromedial medulla (RVM) has a well-documented role in pain modulation and exerts antinociceptive and pronociceptive influences mediated by 2 distinct classes of neurons, OFF-cells and ON-cells. OFF-cells are defined by a sudden pause in firing in response to nociceptive inputs, whereas ON-cells are characterized by a "burst" of activity. Although these reflex-related changes in ON- and OFF-cell firing are critical to their pain-modulating function, the pathways mediating these responses have not been identified. The present experiments were designed to test the hypothesis that nociceptive input to the RVM is relayed through the parabrachial complex (PB). In electrophysiological studies, ON- and OFF-cells were recorded in the RVM of lightly anesthetized male rats before and after an infusion of lidocaine or muscimol into PB. The ON-cell burst and OFF-cell pause evoked by noxious heat or mechanical probing were substantially attenuated by inactivation of the lateral, but not medial, parabrachial area. Retrograde tracing studies showed that neurons projecting to the RVM were scattered throughout PB. Few of these neurons expressed calcitonin gene-related peptide, suggesting that the RVM projection from PB is distinct from that to the amygdala. These data show that a substantial component of "bottom-up" nociceptive drive to RVM pain-modulating neurons is relayed through the PB. While the PB is well known as an important relay for ascending nociceptive information, its functional connection with the RVM allows the spinoparabrachial pathway to access descending control systems as part of a recurrent circuit.


Assuntos
Bulbo/citologia , Vias Neurais/fisiologia , Nociceptores/fisiologia , Dor/patologia , Núcleos Parabraquiais/fisiologia , Potenciais de Ação/efeitos dos fármacos , Anestésicos Locais/uso terapêutico , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Agonistas de Receptores de GABA-A/farmacologia , Temperatura Alta/efeitos adversos , Lidocaína/farmacologia , Masculino , Bulbo/metabolismo , Microinjeções , Muscimol/farmacologia , Vias Neurais/efeitos dos fármacos , Nociceptores/classificação , Nociceptores/efeitos dos fármacos , Dor/tratamento farmacológico , Dor/etiologia , Medição da Dor , Estimulação Física/efeitos adversos , Ratos , Ratos Sprague-Dawley , Ratos Wistar
7.
Stud Hist Philos Biol Biomed Sci ; 42(2): 226-32, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21486661

RESUMO

Absent as a breeding bird from Britain for at least a century, avocets (Recurvirostra avosetta) began nesting on the east coast of Britain, in Suffolk, shortly after the end of the Second World War, having honed in on two spots on Britain's coast that had been flooded for war-related reasons. The avocets' presence was surrounded in secrecy, while a dedicated few kept up a protective watch over them. As the Royal Society for the Protection of Birds (RSPB) took over responsibility for the flourishing colony, they claimed the episode as a symbol of success for British protection, later making the bird their logo. Counter to the RSPB's story of protecting a British bird, I read the narratives of events in terms of making a bird British. I show how, as postwar Britain slumped economically and spiritually and tried to rebuild itself, the birds became a vehicle for formulating national identity: of Britain as a home to which to return and belong. Exploring the themes of returning servicemen and closed territories, the paper also examines the episode in terms of the naturalisation of the military and the militarisation of nature.


Assuntos
Charadriiformes , Conservação dos Recursos Naturais/história , Militares/história , História Natural/história , Animais , História do Século XX , Humanos , Organizações/história , Reino Unido , II Guerra Mundial
8.
Drug Alcohol Depend ; 91(2-3): 236-43, 2007 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17628350

RESUMO

Face validity in animal models of alcohol abuse and dependence is often at odds with robust demonstrations of ethanol-seeking. This study determined the relative influence of ethanol and a flavorant in maintaining ethanol intake in a nonhuman primate model of "cocktail" drinking. Four-year-old male monkeys were maintained on a 6% ethanol/6% Tang solution made available in daily (M-F) 1-h sessions. Experiments determined the effect of (1) a second daily access session, (2) concurrent presentation of the Tang vehicle, (3) sequential presentation of the vehicle in the first daily session and the ethanol solution in the second session, (4) altering the Tang concentration, (5) altering the ethanol concentration, and (6) removal of the flavorant. Mean daily intake (2.7+/-0.2 g/kg/day) was stable over 7 months. Simultaneous availability of a large, but not a low-moderate, volume of the vehicle reduced ethanol intake by about 50%. Decreasing the concentration of Tang in the first daily session reduced ethanol intake, whereas intake of the standard solution was increased in the second session. Ethanol consumption was decreased by only 27% when the flavorant was removed. In summary, alterations that reduced intake in the first daily session resulted in compensatory increases in ethanol intake in the second session, suggesting that animals sought a specific level of ethanol intake per day. It is concluded that models with excellent face validity (flavored beverages) can produce reliable ethanol intake in patterns that are highly consistent with ethanol-seeking behavior.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Etanol/administração & dosagem , Administração Oral , Animais , Comportamento de Escolha , Etanol/sangue , Macaca mulatta , Masculino
9.
Pharmacol Biochem Behav ; 87(1): 11-9, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17475314

RESUMO

RATIONALE: Emergency Department visits and fatalities in which (+/-)3,4-methylenedioxymethamphetamine (MDMA) or (+)methamphetamine (METH) are involved frequently feature unregulated hyperthermia. MDMA and METH significantly elevate body temperature in multiple laboratory species and, most importantly, can also produce unregulated and threatening hyperthermia in nonhuman primates. A majority of prior animal studies have administered drugs by injection whereas human consumption of "Ecstasy" is typically oral, an important difference in route of administration which may complicate the translation of animal data to the human condition. OBJECTIVE: To determine if MDMA and METH produce hyperthermia in monkeys following oral administration as they do when administered intramuscularly. METHODS: Adult male rhesus monkeys were challenged intramuscularly (i.m.) and per os (p.o.) with 1.78 or 5 mg/kg (+/-)MDMA and with 0.1 or 0.32 mg/kg (+)METH. Temperature and activity were monitored with a radiotelemetry system. RESULTS: Oral administration of either MDMA or METH produced significant increases in body temperature. Locomotor activity was suppressed by MDMA and increased by METH following either route of administration. CONCLUSIONS: The data show that the oral route of administration is not likely to qualitatively reduce the temperature increase associated with MDMA or METH although oral administration did slow the rate of temperature increase. It is further established that MDMA reduces activity in monkeys even after relatively high doses and oral administration.


Assuntos
Temperatura Corporal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Metanfetamina/farmacologia , Atividade Motora/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Serotoninérgicos/farmacologia , Administração Oral , Animais , Regulação da Temperatura Corporal/efeitos dos fármacos , Interpretação Estatística de Dados , Injeções Intramusculares , Macaca mulatta , Masculino , Estereoisomerismo , Telemetria
10.
Neuropsychopharmacology ; 32(3): 673-81, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16641942

RESUMO

The ambient temperature (T(A)) under which rodents are exposed to (+/-)3,4-methylenedioxymethamphetamine (MDMA) affects the direction and magnitude of the body temperature response, and the degree of hypo/hyperthermia generated in subjects can modify the severity of lasting brain changes in 'neurotoxicity' models. The thermoregulatory effects of MDMA have not been well described in non-human primates and it is unknown if T(A) has the potential to affect acute hyperthermia and therefore other lasting consequences of MDMA. The objective of this study was to determine if the temperature alteration produced by MDMA in nonhuman primates depends on T(A) as it does in rats and mice. Body temperature and spontaneous home cage activity were monitored continuously in six male rhesus monkeys via radiotelemetry. The subjects were challenged intramuscularly with 0.56-2.4 mg/kg (+/-)MDMA under each of three T(A) conditions (18, 24, and 30 degrees C) in a randomized order. The temperature was significantly elevated following injection with all doses of MDMA under each ambient temperature. The magnitude of mean temperature change was approximately 1 degrees C in most conditions suggesting a closely controlled thermoregulatory response in monkeys across a range of doses and ambient temperatures. Activity levels were generally suppressed by MDMA; however, a 50% increase over vehicle was observed after 0.56 MDMA under the 30 degrees C condition. It is concluded that MDMA produces a similar degree of hyperthermia in rhesus monkeys across a range of T(A) conditions that result in hypothermia or exaggerated hyperthermia in rodents. Monkey temperature responses to MDMA appear to be more similar to humans than to rodents and therefore the monkey may offer an improved model of effects related to MDMA-induced hyperthermia.


Assuntos
Temperatura Corporal/efeitos dos fármacos , Febre/induzido quimicamente , N-Metil-3,4-Metilenodioxianfetamina , Temperatura , Animais , Temperatura Corporal/fisiologia , Regulação da Temperatura Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Macaca mulatta , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Telemetria
11.
Psychopharmacology (Berl) ; 188(4): 586-96, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16538469

RESUMO

RATIONALE: Dopaminergic neurotransmission is critically involved in many aspects of complex behavior and cognition beyond reward/reinforcement and motor function. Mental and behavioral disorders associated with major disruptions of dopamine neurotransmission, including schizophrenia, attention deficit/hyperactivity disorder, Parkinson's disease, Huntington's disease, and substance abuse produce constellations of neuropsychological deficits in learning, memory, and attention in addition to other defining symptoms. OBJECTIVE: To delineate the role dopaminergic D1- and D2-like receptor subtypes play in complex brain functions. MATERIALS AND METHODS: Monkeys (N = 6) were trained on cognitive tests adapted from a human neuropsychological assessment battery (CAmbridge Neuropsychological Test Automated Battery). The battery included tests of spatial working memory (self-ordered spatial search task), visuo-spatial associative memory and learning (visuo-spatial paired associates learning task, vsPAL) and motivation (progressive ratio task, PR). Tests of motor function (bimanual motor skill task, BMS; rotating turntable task, RTT) were also included. The effects of the dopamine D2-like antagonist raclopride (10-56 microg/kg, i.m.) and the D1-like antagonist SCH23390 (SCH, 3.2-56 microg/kg, i.m.) on cognitive performance were then determined. RESULTS: Deficits on PR, RTT, and BMS performance were observed after both raclopride and SCH23390. Spatial working memory accuracy was reduced to a greater extent by raclopride than by SCH, which was unexpected, given prior reports on the involvement of D1 signaling for spatial working memory in monkeys. Deficits were observed on vsPAL performance after raclopride, but not after SCH23390. CONCLUSIONS: The intriguing results suggest a greater contribution of D2- over D1-like receptors to both spatial working memory and object-location associative memory.


Assuntos
Benzazepinas/farmacologia , Antagonistas de Dopamina/farmacologia , Antagonistas dos Receptores de Dopamina D2 , Memória/efeitos dos fármacos , Racloprida/farmacologia , Receptores de Dopamina D1/antagonistas & inibidores , Animais , Atenção/efeitos dos fármacos , Cognição/efeitos dos fármacos , Cognição/fisiologia , Macaca mulatta , Masculino , Motivação , Destreza Motora/efeitos dos fármacos , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia
12.
Drug Alcohol Depend ; 82(3): 276-81, 2006 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-16289931

RESUMO

BACKGROUND: Exposure to (+/-)3,4-methylenedioxymethamphetamine ((+/-)MDMA) results in lasting reductions of many markers for serotonin terminals in a range of species. In rodents, the severity of insult depends in large part on the generation of hyperthermia in the subject. (+/-)MDMA can produce either hyperthermia or hypothermia in rodents depending on the ambient temperature and these effects may be limited to the S(+) enantiomer. Limited prior evidence suggests (+/-)MDMA does not produce hyperthermia in chair-restrained monkeys [Bowyer, J.F., Young, J.F., Slikker, W., Itzak, Y., Mayorga, A.J., Newport, G.D., Ali, S.F., Frederick, D.L., Paule, M.G., 2003. Plasma levels of parent compound and metabolites after doses of either d-fenfluramine or d-3,4-methylenedioxymethamphetamine (MDMA) that produce long-term serotonergic alterations. Neurotoxicology 24, 379-390]. This study was therefore conducted to determine if racemic MDMA and its enantiomers induce hyperthermia and increase spontaneous locomotor activity in unrestrained rhesus monkeys. METHODS: Body temperature and spontaneous home cage activity were monitored continuously in four monkeys via radiotelemetric devices. The subjects were challenged with 1.7 mg/kg, i.m., (+/-)MDMA, S(+)MDMA and R(-)MDMA in pseudorandomized order. RESULTS: Maximum and average temperature in the 4h interval post-dosing was elevated 0.7-0.9 degrees C by (+/-)MDMA and each enantiomer. Reductions in locomotor activity following dosing did not reliably differ from vehicle effects. CONCLUSIONS: MDMA produces an acute hyperthermia in unrestrained rhesus monkeys, much as it does with rats, mice, pigs, rabbits and humans. Hyperthermia occurs despite no increase in locomotor activity thus the effect does not depend on motor activation. Each enantiomer appears to be equivalently active thus primates may differ from rodents in thermoregulatory sensitivity to the R(-) enantiomer. Significant differences in outcome between this and a prior study in monkeys indicate a need for additional study of the thermoregulatory impact of MDMA in nonhuman primates.


Assuntos
Hipertermia Induzida , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Animais , Temperatura Corporal/efeitos dos fármacos , Ritmo Circadiano , Alucinógenos/farmacologia , Macaca mulatta , Masculino , Modelos Animais , Valores de Referência , Restrição Física , Telemetria , Fatores de Tempo
13.
Alcohol Clin Exp Res ; 28(6): 873-83, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15201630

RESUMO

BACKGROUND: Flavorant-fading procedures can initiate and maintain oral ethanol intake in rodents. The present study developed a similar procedure to achieve controlled and behaviorally relevant levels of ethanol intake in monkeys. METHODS: Male rhesus macaques (N = 13) were initially given the opportunity to consume 0.5 g/kg of a 1% (w/v) ethanol plus 4% (w/v) Tang solution in 1-hr limited-access sessions without the requirement of an operant response. Once consumption was stable at a particular concentration (%) and/or amount (g/kg), animals were given access to higher concentrations and/or amounts of ethanol. Animals were tested on a bimanual motor skill (BMS) task 20 and 90 min after consumption to assess behavioral impairment. Blood alcohol levels (BALs) were assessed after a session in which animals had the opportunity to consume up to 3.0 g/kg of 6% (w/v) ethanol. RESULTS: The gradual fading up of higher concentrations and amounts of ethanol resulted in controlled and robust levels (>2.0 g/kg) of ethanol intake in half of the subjects. Increasing the concentration of the sweetener from 4 to 6% (w/v) was effective in initiating consumption in three animals. Two monkeys required the additional step of presenting the increased-sweetener solutions after a meal (postprandial consumption) to initiate significant ethanol intake. Animals were significantly impaired on the BMS task after consumption of 2.0, 2.5, and 3.0 g/kg of ethanol. Individual consumption ranging from 0.8 to 3.0 g/kg of ethanol produced BALs of 18 to 269 mg/dl. CONCLUSIONS: The flavorant-fading procedure was effective in producing behaviorally relevant levels of ethanol consumption in rhesus macaques. This model facilitated a randomized-dose procedure to determine the behavioral effects of 0.5 to 3.0 g/kg of ethanol. This procedure therefore is of significant utility in determining behavioral or physiologic effects of specific doses of consumed ethanol in monkeys.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Etanol/administração & dosagem , Aromatizantes/administração & dosagem , Esquema de Reforço , Administração Oral , Animais , Relação Dose-Resposta a Droga , Macaca mulatta , Masculino , Autoadministração
14.
Behav Brain Res ; 149(2): 123-33, 2004 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-15129776

RESUMO

Early detection of progressive diseases such as Alzheimer's Disease (AD) is crucial for both the treatment and study of the disease. Performance on a visuo-spatial paired-associates learning (vsPAL) task was recently shown to reliably predict a diagnosis of AD in aged populations. The present study reports the development of this vsPAL task for use in nonhuman primates. Translation of vsPAL to a nonhuman model may provide improved preclinical tools for study of the etiology and treatment of dementia. Twelve young adult male rhesus monkeys were trained to perform the vsPAL task concurrently with tests comprising a nonhuman primate neuropsychological test battery. Monkeys successfully learned to perform vsPAL and did so in a task-difficulty ranked fashion. Despite significant individual differences in capability in the acquisition of the recognition memory aspects of the task, all monkeys evidenced the ability to learn within-trial, i.e. to improve with repeated stimulus-location pairings. These results support the use of vsPAL performance under various challenge conditions to investigate the possible substrates of early cognitive decline in AD. Comparison of performance on vsPAL with performance on other memory tasks in the battery will be of more general use in differentiating mechanisms involved in various aspects of mnemonic function.


Assuntos
Doença de Alzheimer/fisiopatologia , Aprendizagem por Associação/fisiologia , Desempenho Psicomotor/fisiologia , Comportamento Espacial/fisiologia , Percepção Visual/fisiologia , Doença de Alzheimer/diagnóstico , Análise de Variância , Animais , Modelos Animais de Doenças , Individualidade , Macaca mulatta , Masculino , Testes Neuropsicológicos , Estimulação Luminosa/métodos , Tempo de Reação , Retenção Psicológica , Análise e Desempenho de Tarefas , Fatores de Tempo
15.
Psychopharmacology (Berl) ; 175(2): 225-40, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15112030

RESUMO

RATIONALE: Nicotine and other agonists of nicotinic cholinergic receptors (nAChR) have been shown to improve performance in specific memory domains in rodents and monkeys. Such beneficial effects are observed in preclinical models of age-related cognitive decline, stimulating interest in nAChR ligands as possible therapeutics. Prior work has typically focused on assays of spatial working memory in rodent studies and visual recognition memory in monkey studies. OBJECTIVE: The current study was conducted to determine the role played by nAChRs in multiple types of memory in monkeys. METHODS: Rhesus monkeys (n=6) were trained to perform a battery of six behavioral tasks and then serially challenged with acute doses of nicotine (3.2-56 microg/kg, i.m.) and the nAChR antagonist mecamylamine (0.32-1.78 mg/kg, i.m.). RESULTS: Nicotine improved performance on tests designed to assay visual recognition memory, spatial working memory and visuo-spatial associative memory, while mecamylamine impaired visuo-spatial associative memory. Ballistic and fine motor performance was not significantly improved by nicotine but fine motor performance was impaired by mecamylamine. CONCLUSIONS: Although nicotine may improve performance in multiple domains, effects on visuo-spatial associative memory is the most specifically attributable to nAChR signaling.


Assuntos
Cognição/efeitos dos fármacos , Mecamilamina/farmacologia , Memória/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Animais , Aprendizagem/efeitos dos fármacos , Macaca mulatta , Masculino , Tempo de Reação/efeitos dos fármacos
16.
Neuropsychopharmacology ; 27(6): 993-1005, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12464456

RESUMO

Recreational users of (+/-)3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") exhibit poor performance on a number of neurocognitive measures, with tests of memory and attention most commonly affected. Cognitive impairments can be persistent or possibly permanent, since users who have been abstinent from MDMA for many months are also impaired. Repeated treatment of rats or nonhuman primates with MDMA has consistently been demonstrated to produce specific, lasting depletions of brain serotonin (5-HT) markers, a potential source of such cognitive symptoms. We have shown, however, that monkeys treated with a regimen of MDMA (4 days, 10 mg/kg i.m., b.i.d.), sufficient to produce a 50% reduction of the 5-HT metabolite 5-hydroxyindoleacetic acid in cerebrospinal fluid, do not exhibit lasting deficits in a range of cognitive domains. Acute drug challenges are often effective at unmasking consequences of amphetamine toxicity. Here, the performance of MDMA-treated and control monkeys on tests of spatial working memory (self-ordered spatial search), vigilance and reaction time (5-choice reaction time), reinforcer efficacy and sustained attention (progressive ratio responding) and fine motor control (bimanual motor skill task) was challenged with ketanserin (0.1-1.7 mg/kg, i.m.), 1-(3-Chlorophenyl)piperazine dihydrochloride (mCPP, 0.03-0.5 mg/kg, i.m.) and (+/-)8-hydroxy-DPAT hydrobromide (8-OH-DPAT, 0.032-0.1 mg/kg, i.m.). MDMA-exposed animals exhibited increased sensitivity to challenge with mCPP on the reaction time and progressive ratio tasks but otherwise were equivalently sensitive to drug challenge. Post-mortem analysis demonstrated that 76-93% reductions of 5-HT in neocortex persist 17-20 months post-MDMA. These observations suggest that large depletions of brain 5-HT produced by MDMA can persistently alter behavioral sensitivity to the disrupting effects of serotonergic agents.


Assuntos
Cognição/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Serotonina/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cognição/fisiologia , Relação Dose-Resposta a Droga , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Ácido Hidroxi-Indolacético/metabolismo , Macaca mulatta , Masculino , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Serotonina/líquido cefalorraquidiano
17.
Drug Alcohol Depend ; 68(2): 175-87, 2002 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-12234647

RESUMO

Available evidence suggests that recreational use and abuse of the dissociative anaesthetic ketamine is increasing. Characterization of the cognitive risks of ketamine exposure contributes substantially to understanding this growing public health threat. Although prior human studies demonstrate that ketamine impairs a range of cognitive skills, investigation in nonhuman models permits more precise exploration of neurochemical mechanisms which may underlie detrimental behavioral effects. Adult male rhesus monkeys (N=7) were trained on a neuropsychological battery including tests of memory (delayed match-to-sample, DMS; self-ordered spatial search, SOSS), reaction time (RT), reinforcer efficacy and sustained attention (progressive ratio, PR) and fine motor coordination (bimanual motor skill, BMS). Battery performance was then serially challenged with acute doses of ketamine (0.3, 1.0, 1.78 mg/kg IM). Ketamine impaired DMS and SOSS in a dose x difficulty dependent manner with the most difficult task conditions disrupted at the 1.0 and 1.78 mg/kg doses. Thus, both visual recognition memory and working memory indices were affected. Ketamine also slowed RT and BMS performance and interfered with PR performance at the 1.78 mg/kg dose. Overall the present findings confirm that ketamine interferes with multiple aspects of cognition at subanesthetic doses in monkeys.


Assuntos
Anestésicos Dissociativos/farmacologia , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Ketamina/farmacologia , Animais , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Macaca mulatta , Masculino , Destreza Motora/efeitos dos fármacos , N-Metilaspartato/metabolismo , Testes Neuropsicológicos , Desempenho Psicomotor/efeitos dos fármacos , Tempo de Reação/efeitos dos fármacos , Análise e Desempenho de Tarefas
18.
Psychopharmacology (Berl) ; 160(3): 253-62, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11889494

RESUMO

RATIONALE: Early, accurate detection of degenerative neurological disorders such as Alzheimer's disease (AD) is essential for therapies designed to slow disease progression. Performance of a touch-screen mediated visuo-spatial paired-associates learning (vsPAL) task predicts neurocognitive decline in elderly populations presenting with mild cognitive impairment and distinguishes AD patients from elderly depressed individuals. Translation of this cognitive task to a non-human model may therefore provide an improved tool for study of the etiology and treatment of dementia. OBJECTIVE: The goal of the current study was to contrast cholinergic and glutamatergic contributions to performance of this AD-sensitive task by challenging rhesus monkeys performing vsPAL with muscarinic antagonist and non-competitive NMDA antagonist drugs. METHODS: Seven monkeys were trained to perform vsPAL and then serially challenged with acute doses of scopolamine (3, 10, 17 microg/kg, IM) and ketamine (0.3, 1.0, 1.78 mg/kg, IM). RESULTS: Scopolamine produced a dosexdifficulty related impairment of both recognition memory and incremental acquisition aspects of task performance. In contrast, ketamine administration resulted in a dose-dependent impairment of recognition memory but not incremental acquisition. CONCLUSIONS: Monkeys' performance of a task sensitive to AD in humans was impaired by two classic pharmacological models of cognitive impairment, therefore supporting the use of this nonhuman model to explore mechanisms of AD-associated cognitive decline. The differential pattern of impairment observed is consistent with a hypothesis that muscarinic mechanisms are required for linking external events with an existing internal representation, whereas NMDA mechanisms are required for the formation/strengthening of such an internal representation.


Assuntos
Aprendizagem por Associação/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas Muscarínicos/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Animais , Aprendizagem por Associação/fisiologia , Relação Dose-Resposta a Droga , Macaca mulatta , Masculino , Estimulação Luminosa/métodos , Desempenho Psicomotor/fisiologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/fisiologia
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