Chronic levetiracetam (Keppra®) treatment increases the reinforcing strength of cocaine in rhesus monkeys.
Pharmacol Biochem Behav
; 207: 173217, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-34116078
ABSTRACT
BACKGROUND:
Drugs that increase inhibitory neuronal activity in the brain have been proposed as potential medications for stimulant use disorders.OBJECTIVE:
The present study assessed the ability of chronically administered levetiracetam (Keppra®), a clinically available anticonvulsant drug that increases GABA by binding to synaptic vesicle glycoprotein 2A, to modulate the reinforcing strength of cocaine in monkeys.METHODS:
Three adult male rhesus monkeys (Macaca mulatta) self-administered cocaine intravenously each day under a progressive-ratio (PR) schedule of reinforcement. Two monkeys also responded to receive food pellets under a 50-response fixed-ratio schedule (FR 50) each morning. After determining a cocaine dose-response curve (0.001-0.3 mg/kg per injection, i.v.) in the evening, levetiracetam (5-75 mg/kg, p.o., b.i.d.) was administered for 12-16 days per dose. To model a treatment setting, cocaine self-administration sessions were conducted using the PR schedule every 4 days during levetiracetam treatment. After tapering the dose of levetiracetam over two weeks in the absence of cocaine sessions, cocaine dose-effect curves were re-determined.RESULTS:
Lower doses of levetiracetam produced non-systematic fluctuations in numbers of cocaine injections received in each subject, whereas the highest tested dose significantly increased the reinforcing strength of cocaine; no effects on food-maintained responding were observed. After termination of levetiracetam treatment, dose-effect curves for cocaine self-administration were shifted to the left in two monkeys.CONCLUSION:
These data suggest that levetiracetam is not likely to be an efficacious pharmacotherapy for cocaine dependence. Rather, sensitivity to cocaine may be increased during and after levetiracetam treatment.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Reforço Psicológico
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Cocaína
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Transtornos Relacionados ao Uso de Cocaína
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Levetiracetam
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Anticonvulsivantes
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article