title: Behavioral evidence for midbrain dopamine depolarization inactivation.
abstract: High (2.5-5 micrograms) doses of ventral tegmental morphine, which normally facilitate brain stimulation reward, were found to cause a complete cessation of bar pressing for brainstem stimulation in animals pretreated with systemic pimozide (0.175-0.35 mg/kg). It was hypothesized that the behavioral failure was due to depolarization inactivation of the dopamine system. Electrophysiological evidence indicates that sufficient doses of morphine or neuroleptics can each cause inactivation by themselves. The behavior was reinstated by ventral tegmental muscimol, which normally suppresses both the behavior and dopamine cell firing but which reinstates dopamine cell firing in depolarization-inactivated cells. This behavioral reinstatement appears to confirm the hypothesis that depolarization inactivation of the dopamine system caused the behavioral failure, and appears to establish depolarization inactivation as a phenomenon of behavioral, and thus potential clinical, importance.
authors.affiliation: Department of Psychology, Concordia University, Montreal, Que., Canada.
authors.forename: P P
authors.initials: PP
authors.lastname: Rompré
authors.forename: R A
authors.initials: RA
authors.lastname: Wise
mesh_terms: D000818:Animals; D004298:Dopamine / Q000502:physiology*; D004347:Drug Interactions; D004558:Electric Stimulation; D008636:Mesencephalon / Q000502:physiology*; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology*; D010868:Pimozide / Q000494:pharmacology*; D051381:Rats; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects*
chemical_list: D010868:Pimozide; D009118:Muscimol; D009020:Morphine; D004298:Dopamine