Effects of the dopamine stabilizer, OSU-6162, on brain stimulation reward and on quinpirole-induced changes in reward and locomotion

TY - JOUR

T1 - Effects of the dopamine stabilizer, OSU-6162, on brain stimulation reward and on quinpirole-induced changes in reward and locomotion

AU - Benaliouad, Faiza

AU - Kapur, Shitij

AU - Natesan, Sridhar

AU - Rompre, Pierre-Paul

PY - 2009/6

Y1 - 2009/6

N2 - 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. (C) 2009 Elsevier B.V. and ECNP. All rights reserved.

AB - 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. (C) 2009 Elsevier B.V. and ECNP. All rights reserved.

U2 - 10.1016/j.euroneuro.2009.01.014

DO - 10.1016/j.euroneuro.2009.01.014

M3 - Article

SN - 1873-7862

VL - 19

SP - 416

EP - 430

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

IS - 6

ER -