title: Neurosteroid allopregnanolone attenuates development of nicotine withdrawal behavior in mice.
abstract: Avoidance of the nicotine withdrawal syndrome as well as the positive subjective effects of nicotine is the major predisposing factor to motivate nicotine abuse. However, its underlying neurobehavioral mechanisms remain perplexing. In the present study, we investigated the influence of the neurosteroid allopregnanolone (ALLO; 0.5-2mg/kg) on the development of nicotine withdrawal in mice. Chronic nicotine injections (2mg/kg, four times daily, 10 days) followed by its withdrawal, elicited severe somatic signs, anxiety and marked reduction in locomotion. However, these withdrawal signs were not evident in animals pretreated with ALLO or progesterone (Day 8-10) daily before 1st injection of nicotine. This effect of neurosteroid on the nicotine withdrawal signs was reversed by indomethacin and finasteride the inhibitors of neurosteroid biosynthesis. On the contrary, single or repeated dose administration of ALLO or progesterone during nicotine withdrawal (Day 11) did not affect the expression of nicotine withdrawal signs. Thus, compounds that modulate endogenous neurosteroid ALLO are likely to have therapeutic potential for treating various aspects of nicotine dependence and withdrawal.
authors.affiliation: Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, Maharashtra, India.
authors.forename: Prajwal P
authors.initials: PP
authors.lastname: Thakre
authors.forename: Meher R
authors.initials: MR
authors.lastname: Tundulwar
authors.forename: Chandrabhan T
authors.initials: CT
authors.lastname: Chopde
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Ugale
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000523:psychology; D018120:Finasteride / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology*; D009538:Nicotine / Q000009:adverse effects*; D011280:Pregnanolone / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000523:psychology*; D013997:Time Factors
chemical_list: D018377:Neurotransmitter Agents; D011374:Progesterone; D018120:Finasteride; D009538:Nicotine; D011280:Pregnanolone; D007213:Indomethacin