GABAB receptors involvement in the effects induced by nicotine on anxiety-related behaviour in mice

BALERIO GRACIELA N.

Barcelona

Conferencia; 2nd International Conference on Addiction Therapy & Clinical Reports; 2019

GABAB receptors involvement in the effects induced by nicotine on anxiety-related behaviour in miceGraciela N. Balerio1,2 1Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Farmacología, Buenos Aires, Argentina.2CONICET - Universidad de Buenos Aires, Instituto de Investigaciones Farmacológicas (ININFA), Buenos Aires, Argentina.Nicotine is the main active component of tobacco. It has both acute and chronic pharmacological effects that can contribute to its potential abuse in humans. Nicotine from tobacco induces stimulation and pleasure and reduces stress and anxiety. These effects of nicotine suggest that the ability of the drug to affect emotionality may be critical to understanding ongoing nicotine use. Since the anxiety is one of the pharmacological effects that contribute to the maintenance of tobacco use, the main goal of the present study was to evaluate the possible involvement of GABAB receptors on the anxiolytic- and anxiogenic-like responses induced by nicotine in mice, using both pharmacological and genetic approaches.Pharmacological approach: In wild-type mice: these results suggests that increased levels of 5-HT in the dorsal raphe and lateral septal nucleus could be responsible, at least in part, in mediating the anxiolytic- and anxiogenic-like effects induced by nicotine, respectively. In addition, the present study revealed that the antagonism of GABAB receptors by 2-OH-saclofen abolished the behavioural responses, neurochemical alterations and c-Fos expression caused by anxiolytic- and anxiogenic-like effect of nicotine in the dorsal raphe and lateral septal nucleus, respectively.Genetic approach: In GABAB1 knockout mice and their wild-type littermates: our results show that the anxiolytic-like effect induced by nicotine was abolished in GABAB1 knockout mice, suggesting the involvement of the GABAB1 subunit in this behavioural response, but not in the anxiogenic-like effect induced by nicotine. In addition, we showed that an increase of 5-HT levels and c-Fos expression in the dorsal raphe and lateral septal nucleus would participate in mediating the anxiolytic- and anxiogenic-like effects induced by nicotine, respectively. On the other hand, these effects were abolished in GABAB1 knockout mice, suggesting the involvement of the GABAB1 subunit in the biochemical alterations induced by both anxiolytic and anxiogenic doses of nicotine. Taken all together, both approaches suggest that GABAB receptors could be involved in the modulation of nicotine-induced anxiety-related behavioral responses in mice. In addition, the present results would provide new findings to support a potential pharmaco therapeutic use of GABAergic drugs in the treatment of tobacco addiction.