Acute restraint stress prevents nicotine-induced mesolimbic dopaminergic activation via a corticosterone-mediated mechanism: A microdialysis study in the rat

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• 作者：Paolo Enrico^a ; ^b ; ^{enrico@uniss.it} ; Donatella Sirca^a ; Maddalena Mereu^c ; Alessandra Tiziana Peana^b ; Beniamina Mercante^a ; Marco Diana^b
• 关键词：Nicotine ; Mesolimbic dopamine system ; Immobilization stress ; Corticosterone ; Microdialysis ; Nicotine
• 刊名：Drug and Alcohol Dependence
• 出版年：2013
• 出版时间：1 January, 2013
• 年：2013
• 卷：127
• 期：1-3
• 页码：8-14
• 全文大小：556 K

文摘

Background

Stress affects the responsiveness to nicotine (NIC), by increasing drug use, facilitating relapse and reinstating NIC self administration even after prolonged abstinence. In turn, high corticosterone (CORT) blood levels induced by stress may alter the neurobiological properties of NIC by acting on the dopamine (DA) mesolimbic system.

Methods

In this study, we evaluated the effect of exposure to acute restraint stress on NIC-induced stimulation of the mesolimbic DA system of the rat, by studying extracellular DA levels in the nucleus accumbens shell (NAccs) with microdialysis.

Results

NIC intravenous administration (130 ¦Ìg/kg) increased DA levels in the NAccs in control rats but not in subjects exposed to stress; this latter phenomenon was prevented by blockade of CORT effects with the inhibitor of corticosterone synthesis metirapone (100 mg/kg) or the glucorticoid receptor antagonist mifepristone (150 ¦Ìmol/kg).

Conclusions

These observations show that exposure to acute stress inhibits the stimulatory response of the mesolimbic DA system to NIC and suggest that this effect is mediated by circulating CORT acting on its receptors. These results may bear relevance in explaining the role played by stressful stimuli in NIC-seeking and taking behavior.