Effects of repeated nicotine administration and footshock stress on rat mesoprefrontal dopamine systems: Evidence for opioid mechanisms

被引:22
作者
George, TP
Verrico, CD
Xu, L
Roth, RH
机构
[1] Yale Univ, Sch Med, Dept Psychiat,Connecticut Mental Hlth Ctr, Div Subst Abuse,Subst Abuse Ctr, New Haven, CT 06519 USA
[2] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA
关键词
nicotine; dopamine; prefrontal cortex; opiates; naloxone;
D O I
10.1016/S0893-133X(99)00165-7
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We have examined the effects of nicotine pl pre-treatment on mesoprefrontal dopamine (DA)function in the presence and absence of acute stress, and the involvement of endogenous opiate peptide systems (EOPS). Acute electrical footshock stress preferentially increases DA utilization in medial prefrontal cortex (mPFC) compared to nucleus accumbens (NAS) and striatal terminal fields, and this is correlated with profound locomotor immobility. Our recent studies have demonstrated that repeated, but not acute, nicotine pre-treatment significantly reduced mPFC DA utilization and footshock stress-induced immobility responses. There is increasing evidence that the biochemical and behavioral effects of nicotine are mediated by EOPS, and we hypothesized that the stress-reducing effects of repeated nicotine administration in these studies were mediated by EOPS. Accordingly, rats pl e-treated subcutaneously with repeated nicotine were given a single dose of the opiate receptor antagonist naloxone (0.1-10.0 mg/kg, i.p.) or saline as a co-treatment with nicotine or saline 10 milt prior to acute footshock stress. Naloxone had Mo effects on non stressed or acute footshock stress-induced mPFC DA utilization, but dose-dependently antagonized repeated nicotine's attenuation of stress-induced mesoprefrontal DA utilization and immobility responses. Furthermore, naloxone dose-dependently blocked repeated nicotine's augmentation of accumbal DA utilization. These results suggest that EOPS may be involved in mediating repeated nicotine administration effects on mesoprefrontal dopaminergic and immobility responses to acute footshock stress. [Neuropsychopharmacology 23:79-88, 2000] (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. All rights reserved.
引用
收藏
页码:79 / 88
页数:10
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