CONICET | Buscador de Institutos y Recursos Humanos

It has been demonstrated that GABAB receptors modulate nicotine (NIC) reward effect; nevertheless, the mechanismimplicated is not well known. In this regard, we evaluated the involvement of GABAB receptors on the behavioral, neurochemical,biochemical and molecular alterations associated with the rewarding effects induced by NIC in mice, froma pharmacological and genetic approach. NIC-induced rewarding properties (0.5 mg/kg, subcutaneously, sc) wereevaluated by conditioned place preference (CPP) paradigm. CPP has three phases: preconditioning, conditioning andpostconditioning. GABAB receptor antagonist 2-hydroxysaclofen (0.25, 0.5 and 1 mg/kg; intraperitoneally, ip) or theGABAB receptor agonist baclofen (3 mg/kg; ip) was injected before NIC during the conditioning phase. GABAB1 knockout(GABAB1KO) mice received NIC during the conditioning phase. Vehicle and wild-type controls were employed.Neurochemical (dopamine, serotonin and their metabolites), biochemical (nicotinic receptor α4β2, α4β2nAChRs)and molecular (c-Fos) alterations induced by NIC were analyzed after the postconditioning phase by high-performanceliquid chromatography (HPLC), receptor-ligand binding assays and immunohistochemistry, respectively, in nucleusaccumbens (Acb), prefrontal cortex (PFC) and ventral tegmental area (VTA). NIC induced rewarding effects in theCPP paradigm and increased dopamine levels in Acb and PFC, α4β2nAChRs density in VTA and c-Fos expression inAcb shell (AcbSh), VTA and PFC. We showed that behavioral, neurochemical, biochemical and molecular alterationsinduced by NIC were prevented by baclofen. However, in 2-hydroxysaclofen pretreated and GABAB1KO mice, thesealterations were potentiated, suggesting that GABAB receptor activity is necessary to control alterations induced byNIC-induced rewarding effects. Therefore, the present findings provided important contributions to the mechanismsimplicated in NIC-induced rewarding effects.