Effects of intra - core administration of MK 801 on serum corticosterone levels in stress-induced reinstatement of cocaine-conditioned animals
DE GIOVANNI, LN; VIRGOLINI, MB; CANCELA, L M
IFEC-CONICET. Departamento de Farmacología. FCQ.UNC
ABSTRACT ar
INTRODUCTION: Drug addiction is considered a chronic and recurrent central nervous system disease; characterized by the reincidence to compulsive drug intake alter a withdrawal period, being this a hallmark of the addiction process. Stress is considered an important factor that induces drug abuse relapse in humans as well as compulsion in cocaine addict behaviors 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. Moreover, several studies demonstrate that nucleus accumbens core are involved in the reinstatement of cocaine-conditioned preference. 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 showed that the systemic and intra-core administration of a non competitive NMDA antagonist, MK 801, blocked the restraint stress-induced reinstatement in extinguished cocaine-induced conditioned place preference (CPP) in rats. Also, we demonstrate that the systemic administration of MK 801 enhanced serum corticosterone levels, suggesting that the serum corticosterone levels does not influence the blockade of stress- induced reinstatement in extinguish cocaine-conditioned animals, however the influence that MK 801 administered in nucleus accumbens core does not determined, yet.
OBJECTIVE: In the current experiments were performed to determine if corticosterone, the principal hormone released in response to stress, influence the effect of the intra-core administration of MK 801 on restraint stress-induced reinstatement.
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 injected with MK 801 (0.1 mg/kg i.p.) or were mircoinfuded intra-core with MK 801 (0.75 ug/side) 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. All groups were then tested in the CPP, and their blood collected for serum corticosterone determination.
RESULTS: We demonstrate that, in the systemic administration MK 801 enhanced serum corticosterone levels in SA and CA. However its effect was not observed for the intra-core administration. These results show that the blockage of stress-induced reinstatement by MK 801 administration is not dependent on the corticosterone response.
DISCUSSION: The current results support our previous results where we demonstrate that, the blockade or stress-induced reinstatement induced by MK 801 is not dependent of the effect that these lingands exerts in serum corticosterone levels. Moreover the intra-core administration of MK 801 did not influence the serum corticosterone levels supporting the hypothesis of the non-corticosterone dependent effect of MK 801 in stress- induced reinstatement in extinguish-cocaine conditioned animals.
Cocaine, Stress-induced reinstatement; NMDA receptors- Corticosterone- Nucleus Accumbens Core.
