Neurosteroid Allopregnanolone Attenuates Development of Nicotine Withdrawal Behavior in Mice

The study investigated the effects of the neurosteroid allopregnanolone (ALLO) on nicotine withdrawal in mice. Mice subjected to chronic nicotine injections exhibited severe withdrawal symptoms, including somatic signs, anxiety, and reduced locomotion. However, pretreatment with ALLO or progesterone significantly mitigated these symptoms, an effect reversed by inhibitors of neurosteroid biosynthesis. ALLO administration during withdrawal did not affect withdrawal signs, suggesting its role in the development of nicotine dependence rather than withdrawal expression. The findings indicated that ALLO could be a potential pharmacological target for preventing nicotine relapse.