Acute restraint stress prevents nicotine-induced mesolimbic dopaminergic activation via a corticosterone-mediated mechanism: a microdialysis study in the rat.
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 μg/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 μmol/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.
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy. enrico@uniss.it
Paolo
P
Enrico
Donatella
D
Sirca
Maddalena
M
Mereu
Alessandra Tiziana
AT
Peana
Beniamina
B
Mercante
Marco
M
Diana
D000818:Animals; D003345:Corticosterone / Q000097:blood*; D004298:Dopamine / Q000378:metabolism*; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D015735:Mifepristone / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000097:blood* / Q000523:psychology
D015735:Mifepristone; D009538:Nicotine; D004298:Dopamine; D003345:Corticosterone