Baclofen Reversed the Nicotine-Induced Anxiety- Like Behavior: A Beneficial Therapeutic Strategy for Smoking Cessation Aid

Background: Nicotine dependence is the most widespread form of substance abuse. Anxiety is one of the prominent symptoms in withdrawal syndromes of nicotine. Nucleus Accumbens (NAc) is a principle area which participates in several behavioral responses (e.g., anxiety), and several studies reported that receptors are involved in the modulation of anxiety. This study was aimed to examine the interaction of baclofen and nicotine on anxiety behavior in NAc shell. Materials and Methods: Rats weighing between 220 and 250g were used. The guide cannulas were implanted bilaterally into the shell of the NAc. Nicotine (0.025, 0.05 and 0.5 μg/rat) and baclofen (0.25, 0.5 and 2 μg/rat) and the co-administration of nicotine (0.025, 0.05 and 0.5μg/ rat) with baclofen (0.25 μg/rat) were microinjected through the infusion cannula. The elevated plus-maze (EPM) was used to evaluate the anxiety-like parameters, and all data were recorded and analyzed. Results: Intra-NAc administration of nicotine (0.5μg/rat) decreased anxiety (P< 0.001). Microinjections of baclofen (0.5 and 2 μg/rat) decreased anxiety (P< 0.001). However, there were no significant changes in anxiety-like parameters at the lowest dose of baclofen (0.25μg/rat). Co-administration of an ineffective dose of baclofen (0.25 μg/rat) with 3 doses of nicotine (0.025, 0.05 and 0.5 μg/rat) reversed the effects of nicotine in an effective dose (0.5 μg/rat). Conclusion: Our result indicated that GABAergic agonist baclofen in ineffective doses could reverse the effects of nicotine on anxiety symptoms. Furthermore, our result suggested that enhancement of GABA transmission through activation of GABA-B receptors on NAc shell could reverse nicotine anxiety-related effects. It may be a strategy of treatment for smoking cessation aid.