title: Effect of ventral tegmental 6-hydroxydopamine lesions on the locomotor stimulant action of nicotine in rats.
abstract: Convergent evidence suggests that the locomotor stimulant effect of nicotine is mediated by nicotinic receptors located on mesolimbic dopaminergic neurons. However, 6-hydroxydopamine lesions of the ventral tegmental area, resulting in substantial depletion of nucleus accumbens dopamine, were recently reported to have no effect on nicotine-induced locomotion. The present study sought to re-examine this issue. Rats received bilateral infusions of 6-hydroxydopamine or vehicle into the ventral tegmental area. Starting 3 weeks later, locomotor activity was tested after subcutaneous injection of saline, nicotine (0.4 mg/kg base), amphetamine (0.5 mg/kg) or scopolamine (0.5 mg/kg). In lesioned animals, the locomotor stimulant effects of nicotine and amphetamine were greatly reduced, whereas saline and scopolamine-induced activity was scarcely affected. Dopamine denervation was assessed by autoradiography, using [125I]RTI-55 to label plasmalemmal dopamine transporters. Labelling was reduced in nucleus accumbens core and shell and in the ventral tegmental area (by 87, 81 and 70%, respectively), and in nigrostriatal areas (52-77%). The locomotor stimulant effects of nicotine and amphetamine were correlated with residual [125I]RTI-55 labelling in mesolimbic and nigrostriatal regions (r=0.6-0.8). The present results provide further evidence that the locomotor stimulant effect of nicotine is dependent on the integrity of ascending dopamine neurons.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Louis
authors.forename: P B
authors.initials: PB
authors.lastname: Clarke
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D002352:Carrier Proteins / Q000378:metabolism; D002421:Caudate Nucleus / Q000502:physiology; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003714:Denervation; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000502:physiology; D016627:Oxidopamine; D011699:Putamen / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology; D013681:Tegmentum Mesencephali / Q000473:pathology / Q000502:physiology*; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D009538:Nicotine; D016627:Oxidopamine; D000661:Amphetamine; D012601:Scopolamine; D003042:Cocaine; D004298:Dopamine