Involvement of cannabinoid CB1 receptors of nucleus accumbens core in stress-induced reinstatement in extinguished cocaine-conditionated animals

GUZMAN, A.S.; DE GIOVANNI, L.N.; VIRGOLINI, M.B.; CANCELA, L.M.

Congreso; Reunión Nacional - III Encuentro Internacional Asociación Argentina de Ciencias del Comportamiento; 2013

INVOLVEMENT OF CANNABINOID CB1 RECEPTORS WITHIN NUCLEUS ACCUMBENS CORE IN STRESS-INDUCED REINSTATEMENT IN EXTINGUISHED COCAINE?CONDITIONED ANIMALS.   GUZMAN, A.S.; DE GIOVANNI, L.N.; VIRGOLINI, M.B.; CANCELA, L.M. IFEC-CONICET. Departamento de Farmacología. FCQ.UNC andreasuguz@gmail.com   ABSTRACT INTRODUCTION: Relapse to drug abuse after long periods of abstinence is a common feature of drug addiction. Stress is considered an important factor that induces drug abuse relapse in human that can be modeled in laboratory animals. At this respect, it has been demonstrated that an acute stress exposure during cocaine withdrawal induced cocaine compulsion in reinstatement in drug-associated contexts. One of the paradigms widely used in laboratory animals to study the relapse to compulsive drug intake is the reinstatement of the cocaine conditioned place preference. Previous results from our lab demonstrated that in extinguished cocaine-conditioned animals evaluated in a conditioned place preference test (CPP), the restraint stress was able to reinstate the cocaine conditioned place preference. In relation to the neurotransmission systems involved in these behaviors, there are evidences related to the participation of glutamatergic in relevant neural circuits for the drug action and stress impact on addiction. Moreover, several studies suggested that nucleus accumbens core is one of mesocorticolimbic brain regions involved in the reinstatement in cocaine-conditioned animals. More recently an influence of endocannabinoid system on the effects that glutamatergic pathway exerts in cocaine reward has been shown. OBJECTIVE: The current experiments were performed to determine whether the endocannabinoid system influence the restraint stress-induced reinstatement in extinguished cocaine-conditioned animals. MATERIALS AND METHODS: Male Wistar rats (220-300g) were conditioned with cocaine (10 mg/kg i.p.) during four alternated drug/vehicle sessions, and later extinguished with successive vehicle associations. On the reinstatement day, animals were microinfuded intra-core with a CB1 receptor antagonist, AM 251 (0, 5 or 10 ug/side) or vehicle (VEH), and subsequently assigned to the following treatments: 1) Stressed animals (SA): 30 min-restraint exposure, and 2) Control animals (CA): left undisturbed in their home cages. Then, all groups were tested in the CPP apparatus. RESULTS: The administration of AM 251 abrogated the restraint stress-induced reinstatement in extinguished cocaine-conditioned animals. DISCUSSION: Our results support the hypothesis of the influence of CB1 receptors in cocaine reward, particularly, in restraint stress-induced reinstatement in extinguished cocaine-conditioned animals. Additional experiments will be performed to study a possible influence of CB1 receptors in the restraint stress-induced changes on the glutamatergic neurotransmission in nucleus accumbens core.    Keywords: Restraint stress induced reinstatement; CB1 receptors; Cocaine; Nucleus Accumbens Core.