title: Effects of the dopamine stabilizer, OSU-6162, on brain stimulation reward and on quinpirole-induced changes in reward and locomotion.
abstract: Dysregulation of limbic dopamine (DA) neurotransmission results in abnormal positive or negative emotional states that characterize several mental disorders. Drugs that restore DA homeostasis are most likely to constitute effective treatments for such emotional disturbances. In this study, we investigated the effects of several doses of OSU-6162, a drug that belongs to a new class named "DA stabilizers", on brain stimulation reward. Because quinpirole produces, depending on the dose, a pre-synaptic depressant and a post-synaptic stimulatory effect on reward and locomotor activity, we also compared the ability of OSU-6162 and haloperidol to prevent these effects of the full DA agonist. Results show that OSU-6162 produced a dose-orderly reduction of reward with no change in the capacity of the animals to produce the operant response, and prevented, like haloperidol, both stimulatory and depressant effects of quinpirole on locomotor activity but only its reward stimulatory effect. The observed functional antagonism of OSU-6162 on these DA-dependent behaviors suggests that it may constitute an effective treatment for abnormal positive emotional state, and that it would be exempt of motor side-effects.
authors.affiliation: Centre de recherche Fernand-Seguin de l'Hôpital Louis-H. Lafontaine Montréal, Canada; Département de physiologie, Université de Montréal, Montréal, Canada.
authors.forename: Faïza
authors.initials: F
authors.lastname: Benaliouad
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: Sridhar
authors.initials: S
authors.lastname: Natesan
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Rompré
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects; D046690:Deep Brain Stimulation / Q000379:methods; D015259:Dopamine Agents / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012646:Self Administration; D013997:Time Factors
chemical_list: D015259:Dopamine Agents; D010880:Piperidines; C109513:OSU 6162; D019257:Quinpirole; D006220:Haloperidol