Involvement of cannabinoid CB1 within nucleus accumbens core but not shell in stress-induced reinstatement in extinguished cocaine-conditioned animals

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

Valparaiso

Simposio; Symposium NuMIND "Biology of Neuropsychiatric Disorders; 2016

Relapse to drugabuse is acommon feature of drug addiction. Stress is considered an importantfactor that induces relapse in human andcan be modeled in laboratory animals. Previousresults in our lab have demonstrated that in animals evaluatedin a conditionedplace preference (CPP) paradigm, an acute restraint stress exposure triggersreinstatementof cocaine-CPP. In respect to the neurotransmission systemsinvolved in these behaviors, there areevidences related to the participationof endocannabinoid system, primarily through their actions at CB1receptors(CB1R), in relapse to drug seeking. Moreover, several studies suggested thatNucleus Accumbens(NAc) is one of the main mesocorticolimbic brain regioninvolved in the drug and stress impact on addiction.The present study has beendesigned to evaluate the involvement of CB1R within both compartments of NAc,Coreand Shell, in restraint stress?induced reinstatement model. Male Wistar rats(220-300g) that extinguishedcocaine-CPP were microinjected into the Core orinto the Shell of NAc with a CB1R agonist (ACEA; 0.001or 0.01fmol/side), aCB1R antagonist (AM251; 5 or 10ug/side) or vehicle, subsequently assigned tothefollowing treatments and then tested in the CPP apparatus: 1) StressedAnimals (SA): 15 or 30 min-restraintexposure, depending on the experiment, and2) Control Animals (CA). Results show that the intra-Coreadministration ofAM251 abrogated restraint stress-induced reinstatement, and ACEA facilitatedreinstatementafter a non-reinstatement stress exposure (15 min). Interestingly,these effects of CB1R ligands after intra-Core administration were not observedafter CB1R ligands microinjection into the Shell compartment. Ourresultssupport the hypothesis of the preferential influence of CB1R within NAc Core,but not Shell, in thereinstatement of cocaine seeking behavior. Thisconclusion is in accordance with previous results of ourlab that demonstratethe preferential role of glutamatergic transmission within NAc Core in the samemodel.Futures studies will attempt to confirm a possible glutamate dependentmechanism underpinning the effectsof CB1R ligands on the restraintstress-induced reinstatement of cocaine-CPP responses.