Rationale: Neuronal nicotinic acetylcholine receptors (nAChRs) are implicated in the reinforcing effects of nicotine and ethanol. Previous studies have shown that cytisine and its 5-bromo derivative are partial agonists at the α4β2 nAChRs and that the parent molecule cytisine is effective in reducing both nicotine- and ethanol-self-administration in rats. However, whether 5-bromocytisine affects nicotine or ethanol self-administration was unknown.
Objectives: The present study compared the effects of 5-bromocytisine and cytisine on nicotine self-administration and further assessed the effect of daily drug injection on voluntary ethanol consumption in alcohol-preferring female rats. Animals were administered a 1.5mg/kg i.p. dose of 5-bromocytisine or cytisine every day for 15-16 days.
Results: The initial efficacy of 5-bromocytisine and cytisine in reducing nicotine intake was similar (-80%) while for voluntary ethanol intake 5-bromocytisine was a superior inhibitor over cytisine (-78% and -40% respectively). The efficacy of cytisine began to diminish after 10 days of daily administration, which was attributed to tolerance development to its inhibitory effects both on nicotine and ethanol self-administration. Tolerance did not develop for 5-bromocytisine.
Conclusion: 5-Bromocytisine, a weaker α4β2 nAChR partial agonist than cytisine, also produces a sustained inhibition of both nicotine and ethanol self-administration, and unlike cytisine, it does not develop tolerance.
Keywords: 5-Bromocytisine; Cytisine; Ethanol; Nicotine; Rats.
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