THE NMDA ANTAGONIST MK-801 BLOCKS STRESS-INDUCED REINSTATEMENT IN THE CONDITIONED PLACE PREFERENCE MODEL
De Giovanni Laura Noemi1, Virgolini Miriam Beatriz1, Cancela Liliana Marina1
1, Virgolini Miriam Beatriz1, Cancela Liliana Marina11IFEC-CONICET. Dpto de Farmacología, Facultad de Ciencias Químicas, UNC, Córdoba, Argentina.
IFEC-CONICET. Dpto de Farmacología, Facultad de Ciencias Químicas, UNC, Córdoba, Argentina.In previous results we have showed that using the conditioned
place preference procedure, a single 30-min immobilization stress session
induces the reinstatement of cocaine seeking behavior in animals previously
conditioned with this drug. Moreover, we have also demonstrated that 72
hours after the reinstatement test, these animals reinstate again after a
priming dose of cocaine. Based on recent research that suggests that
the NMDA antagonist, MK 801, blocks cocaine-induced reinstatement,
we aimed to prove that this blockade is also present after stress-induced
reinstatement, providing at the same time further evidence for the shared
neurobiological mechanisms between stress and cocaine. Male Wistar
rats were injected with cocaine 10-mg/kg ip and confined to one of two
compartments in four alternated daily sessions drug/vehicle; being the
preference for each context later evaluated. The extinction phase consisted
in successive associations with vehicle in both compartments. Reinstatement
was evaluated measuring the time spent in each compartment after 30 min
of immobilization stress and, 72 h later, in response to a cocaine priming
injection (5 mg/kg). We demonstrated that a systemic injection of MK 801
(0.01 or 0.02 mg/kg) administered 15 minutes before the stress session,
blocked stress-induced reinstatement and that this blockade persisted for
at least 72 hours when was evaluated in response to a cocaine priming
injection. These results support the hypothesis of a potential role of the
NMDA receptor in the cocaine seeking behaviour induced by stress or
cocaine. Further experiments are designed to identify the contribution of
the reward and memory processes in the long-lasting MK-801 disruptive
effects in addiction