Levo-tetrahydropalmatine attenuates cocaine self-administration under a progressive-ratio schedule and cocaine discrimination in rats.
Pharmacol Biochem Behav
; 97(2): 310-6, 2010 Dec.
Article
en En
| MEDLINE
| ID: mdl-20816889
ABSTRACT
Levo-tetrahydropalmatine (l-THP) is an alkaloid found in many traditional Chinese herbal preparations and has a unique pharmacological profile that includes dopamine receptor antagonism. Previously we demonstrated that l-THP attenuates fixed-ratio (FR) cocaine self-administration (SA) and cocaine-induced reinstatement in rats at doses that do not alter food-reinforced responding. This study examined the effects of l-THP on cocaine and food SA under progressive-ratio (PR) schedules of reinforcement and the discriminative stimulus effects of cocaine. In adult male Sprague-Dawley rats self-administering cocaine (0.5 or 1.0mg/kg/inf), l-THP significantly reduced breaking points at the 1.875, 3.75 and 7.5mg/kg doses. l-THP also reduced the breaking point and response rate for PR SA of sucrose-sweetened food pellets, although the decrease was significant only at the 7.5mg/kg l-THP dose. In rats trained to discriminate cocaine (10mg/kg, ip) from saline, l-THP (1.875, 3.75 and 7.5mg/kg) produced a rightward shift in the dose-response curve for cocaine generalization. During generalization testing, l-THP reduced response rate, but only at the 7.5mg/kg dose. l-THP also prevented substitution of the dopamine D2/D3 receptor agonist, (±) 7-OH-DPAT, for cocaine suggesting a potential role for antagonism of D2 and/or D3 receptors in the effects of l-THP. These data further demonstrate that l-THP attenuates the reinforcing and subjective effects of cocaine at doses that do not produce marked motor effects and provide additional evidence that l-THP may have utility for the management of cocaine addiction.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Alcaloides de Berberina
/
Cocaína
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Inhibidores de Captación de Dopamina
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Adrenérgicos
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Condicionamiento Operante
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Trastornos Relacionados con Cocaína
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Discriminación en Psicología
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Pharmacol Biochem Behav
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos