title: Nicotine-induced increase of dopaminergic mesoaccumbal neuron activity is prevented by acute restraint stress. In vivo electrophysiology in rats.
abstract: Stress is well known to affect responsiveness to drugs of abuse and influencing approaching and drug-taking behaviour in both animals and humans. Consistently, in nicotine addicted subjects both negative events and perceived stress levels are reported to increase drug use and facilitate relapse to smoke even after long periods of abstinence. It has been suggested that stressful stimuli may influence the rewarding properties of abused drugs by acting on the dopaminergic mesolimbic system. In line with this hypothesis, a recent microdialysis study in rats has shown that acute restraint stress exposure prevents the nicotine-induced mesolimbic dopaminergic activation in the nucleus accumbens (NAC) shell via a corticosterone-mediated mechanism. In the present study we sought to evaluate the impact of acute restraint stress on nicotine-induced activation of the mesoaccumbal dopaminergic system by extracellular single unit recordings of antidromically-identified NAC shell projecting dopaminergic neurons within the ventral tegmental area (VTA). Nicotine intravenous administration dose-dependently (0.05-0.4mg/kg) stimulated the spontaneous firing and bursting of mesoaccumbal dopaminergic neurons in unstressed rats, as previously reported. By contrast, nicotine failed to increase mesoaccumbal dopaminergic neuron activity in rats previously exposed to 1-h immobilisation stress. Our observations show that acute restraint stress inhibits the response of the mesoaccumbal dopaminergic system to the stimulating properties of nicotine. These findings corroborate the notion that stress reduces the sensitivity to nicotine and suggest that the decreased dopaminergic release in the NAC shell is due to a reduced firing and bursting activity in the VTA.
authors: "G. Minardi" Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy; Brain Repair Centre, University of Cambridge, CB2 0PY Cambridge, United Kingdom. Electronic address: fp303@cam.ac.uk.
authors: Francesca
authors: F
authors: Panin
authors: "G. Minardi" Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy; Neuroheuristic Research Group, University of Lausanne, Lausanne, Switzerland.
authors: Alessandra
authors: A
authors: Lintas
authors: "G. Minardi" Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy.
authors: Marco
authors: M
authors: Diana
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D009538:Nicotine
keywords: Electrophysiology; Mesoaccumbal dopaminergic system; Nicotine; Restraint stress