GABAB receptors involvement in the behavioral and neurochemical consequences induced by nicotine rewarding properties in mice: pharmacological and genetic approaches

VARANI A.P.; PEDRÓN V.T.; BETTLER B.; BALERIO G.N.

Milán

Congreso; 9th FENS Forum of European Neuroscience; 2014

FENS

GABAB receptors involvement in the behavioral and neurochemical consequences induced by nicotine rewarding properties in mice: pharmacological and genetic approaches. Varani A.P.a, Pedrón V.T.a, Bettler B.b and Balerio G.N.a,c aININFA (UBA-CONICET), bPharmazentrum (UNIBASEL), cCát. de Farmacología (FFyB-UBA). Junín 956 5° Piso, Buenos Aires C1113AAD, Argentina. avarani@ffyb.uba.ar Introduction: Nicotine (NIC) is the primary psychoactive substance in tobacco smoke which in turn it is responsible for the rewarding effects. Aims: To evaluate the possible GABAB receptors involvement in the behavioral and neurochemical consequences induced by NIC rewarding properties in mice, using both pharmacological and genetic approaches. Methodology: NIC rewarding properties (0.5 mg/kg, sc) were evaluated by the conditioned place preference (CPP) paradigm. The CPP has three phases: pre-conditioning, conditioning and post-conditioning. For the pharmacological approach, 2-OH-saclofen (SAC, GABAB receptor antagonist, 1 mg/kg, ip) or baclofen (BAC, GABAB receptor agonist, 3 mg/kg, ip) was injected before NIC during the conditioning phase. For the genetic approach, GABAB1 knockout (KO) mice received NIC during the conditioning phase. The neurochemical alterations (dopamine, serotonin and their metabolites DOPAC and 5-HIAA, respectively) induced by NIC (0.5 mg/kg, sc) were analyzed by HPLC in accumbens nucleus (Acb), prefrontal cortex (PFC) and ventral tegmental area. Results: NIC (0.5 mg/kg, sc) induced rewarding effects in the CPP paradigm. BAC decreased while SAC or the lack of GABAB receptors (KO) increased NIC rewarding properties in the CPP. In addition, NIC (0.5 mg/kg, sc) increased dopamine levels in the Acb and PFC while the DOPAC levels were increased in the Acb. These neurochemical alterations induced by NIC, decreased in BAC-pretreated mice and increased in SAC-pretreated and KO mice. Conclusions: The behavioral and neurochemical consequences induced by NIC rewarding properties could be modulated by the GABAB receptors activity. Supported by Grants UBACyT 20020120100244BA and PIP 11420090100303