Effects of fendiline on cocaine-seeking behavior in the rat.
Psychopharmacology (Berl)
; 232(24): 4401-10, 2015 Dec.
Article
en En
| MEDLINE
| ID: mdl-26345344
ABSTRACT
RATIONALE L-type Ca(2+) channels (LTCC) and GABAB receptors are both possible targets in the development of new pharmacological compounds for cocaine addiction. Drugs that target either receptor attenuate a wide range of cocaine-seeking behaviors in the rat. However, there is no current human-approved pharmacotherapeutic intervention for psychostimulant addiction. OBJECTIVES:
This study examined the effects of a human-approved LTCC blocker, fendiline, on cocaine-taking and cocaine-seeking behavior in rats. The effects of combining fendiline with the GABAB receptor agonist baclofen on cocaine self-administration were also tested.METHODS:
Male Wistar rats were trained to self-administer cocaine, and the effects of fendiline pretreatment (vehicle, 1.78, 3.16, 5.62 mg/kg, intraperitoneal (IP)) were tested on progressive ratio responding and cue- and drug-induced reinstatement. The effects of baclofen (vehicle, 0.56, 1.78, 3.16, 5.62 mg/kg, IP) combined with fendiline (5.62 mg/kg, IP) were tested on progressive ratio responding. Control experiments measured locomotor activity and lever pressing for food in rats that received both baclofen and fendiline prior to the test session.RESULTS:
Acute injections of fendiline prior to cue- or drug-induced reinstatement significantly attenuated lever-pressing behavior (p < 0.05). Fendiline and baclofen, but not fendiline alone, not only significantly attenuated breakpoints, but also impaired general motor behavior and naturalistic reinforcement (p < 0.05).CONCLUSION:
These data suggest that the LTCC blocker fendiline may represent a novel pharmacotherapeutic intervention to prevent reinstatement to cocaine seeking. Also, co-administration of fendiline and baclofen not only can attenuate the motivation to take cocaine, but also impairs general motor behavior and naturalistic reinforcement.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Bloqueadores de los Canales de Calcio
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Fendilina
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Cocaína
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Comportamiento de Búsqueda de Drogas
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Estimulantes del Sistema Nervioso Central
Límite:
Animals
Idioma:
En
Revista:
Psychopharmacology (Berl)
Año:
2015
Tipo del documento:
Article
País de afiliación:
Canadá