GABAB receptors involvement in the modulation of the behavioral, neurochemical, biochemical and molecular alterations induced by nicotine rewarding effect: Pharmacological and genetic approaches

BALERIO GRACIELA N.; VARANI ANDRÉS P.; PEDRÓN VALERIA T.; AON, AMIRA J.; HÖCHT CHRISTIAN; BETTLER BERNHARD

Congreso; 10th FENS Forum of Neuroscience; 2016

We evaluated the involvement of GABAB receptors in the behavioral, neurochemical, biochemical and molecular alterations associated to the rewarding effect induced by nicotine (NIC) in mice, using both pharmacological and genetic approaches. NIC rewarding properties were evaluated by the conditioned place preference (CPP) paradigm. The CPP has three phases: pre-conditioning, conditioning and post-conditioning. Pharmacological approach: the GABAB receptor antagonist 2-OH-saclofen (SAC 0.25, 0.5 and 1 mg/kg; ip) or the GABAB receptor agonist baclofen (BAC 3 mg/kg; ip) were injected before NIC during the conditioning phase. Genetic approach:GABAB1 knockout (GABAB1 KO) mice received NIC during the conditioning phase. Neurochemical (dopamine, serotonin and their metabolites), biochemical (nicotinic receptor á4â2) and molecular alterations (c-Fos) induced by NIC (0.5 mg/kg, sc) were analyzed after the post-conditioning phase by HPLC, receptor-ligand binding assays and immunohistochemistry, respectively, in the accumbens nucleus (Acb), prefrontal cortex (PFC) and ventral tegmental area (VTA). The results revealed that NIC induced rewarding effects in the CPP paradigm, and increased dopamine levels in the Acb and PFC, nicotinic receptor á4â2 density in the ATV and c-Fos expression in the Acb Shell, ATV and PFC. Importantly, the activation of GABAB receptors showed that behavioral, neurochemical, biochemical and molecular alterations induced by NIC were prevented in BAC-pretreated mice, however, these alterations were potentiated in SAC-pretreated and GABAB1KO mice. Our results suggest that GABAB receptor activity could modulate changes induced by NIC rewarding effect. In conclusion, GABAB receptors could be consider as a promising target to prevent the rewarding effect induced by NIC.