Neurosteroid allopregnanolone attenuates development of nicotine withdrawal behavior in mice.
Neurosci Lett
; 541: 144-9, 2013 Apr 29.
Article
in En
| MEDLINE
| ID: mdl-23485740
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.
Full text:
1
Database:
MEDLINE
Main subject:
Pregnanolone
/
Substance Withdrawal Syndrome
/
Neurotransmitter Agents
/
Nicotine
Limits:
Animals
Language:
En
Year:
2013
Type:
Article