Basolateral amygdala and ventral hippocampus in stress-induced amplification of nicotine self-administration during reacquisition in rat

Rationale Cigarette smoking remains the leading cause of preventable morbidity and mortality in the USA, although only 3–5 % of quitters are successful for 6–12 months. Stress during abstinence increases the likelihood of relapse to smoking. We recently reported that repeated stress during abstinence from operant nicotine self-administration (SA) amplifies the reacquisition of nicotine SA and affects the diurnal intake of nicotine in rats. Herein, we sought to identify brain regions critical for the expression of stress-enhanced nicotine SA during reacquisition. Methods Rats acquired nicotine SA (FR5) with virtually unlimited drug access (23 h/day). During abstinence (8 day), 30 min of restraint stress was applied on days 1, 3, 5, and 7. Beginning day 8, nicotine SA was reacquired over 5 days, and basolateral amygdala (BLA) was inactivated bilaterally or disconnected from nucleus accumbens core (NAcc). Similarly, ventral hippocampus (vHP) was inactivated or disconnected from BLA. Results Bilateral inactivation (muscimol + baclofen) of BLA or disconnection from NAcc abolished the stress-enhanced reacquisition of nicotine SA without affecting basal levels of nicotine SA. Similarly, bilateral inactivation of vHP or disconnection of vHP and BLA also abolished stress-enhanced reacquisition of nicotine SA. Conclusion BLA, vHP, and functional interactions between BLA-NAcc and vHP-BLA are required for expression of stress-enhanced nicotine SA during reacquisition. However, without stress, these functional interactions are not necessary for reexpression of nicotine SA during reacquisition. Therefore, BLA, vHP, and these regional interactions specifically mediate the effects of repeated stress on the reacquisition of nicotine SA behavior.