Recent studies from our lab have demonstrated that the administration of the NMDA antagonist, MK-801, before a single immobilization-stress blocked the stress-induced reinstatement to cocaine in cocaine-conditioned animals. The goal of this study was to study whether the blocking effect of MK-801 on the development of stress-induced reinstatement, was also observed in the expression of this phenomenon. Male Wistar rats (220-300 g) were conditioned with daily cocaine injections (10-mg/kg ip), and confined to one of two compartments during four alternated drug/vehicle sessions, being the preference for each context later evaluated. Thereafter, the preference of the animals for a given context was extinguished with successive vehicle associations in both compartments. In the reinstatement day, the animals were separated in two groups: non-stress and stress (30 min immobilization). After finished the stress protocol, the animals were immediately placed back in their home cages, received MK-801 (0.1 mg/kg ip) or VEH, and tested 15 min later in the conditioned place preference paradigm (CPP). We observed that the MK-801 pre-administration blocked the expression of stress-induced reinstatement as we have previously described for the development of this phenomenon. In addition, the blockade of the two subsequent cocaine-induced reinstatement tests, observed either in the MK-non-stress or the MK-stress groups, indicates a long-lasting effect of MK-801. These results provide evidences that, glutamatergic mechanisms activated immediately after the end of the stress, are implied in the expression of the stress-induced reinstatement in the CPP. Finally, these findings further support the hypothesis of an interchangeability in the mechanisms underlying the stress and cocaine-induced reinstatement.
Financial Support: FONCyT, SECyT, CONICET
