title: Enhanced reward-facilitating effects of d-amphetamine in rats in the quinpirole model of obsessive-compulsive disorder.
abstract: The underlying neurobiology of addictive or repetitive behaviours, such as obsessive-compulsive disorder (OCD), involves dopaminergic dysregulation. While addictive behaviour depends strongly on mesolimbocortical dopaminergic responses, repetitive behaviours have been associated with dopaminergic dysregulation in the basal ganglia-thalamo-cortical circuitry. The present study investigates differences in brain stimulation reward in rats with quinpirole-induced compulsive checking behaviour, in order to examine if deficits in reward processing are also relevant for OCD. Rats were tested in the intracranial self-stimulation (ICSS) paradigm, which targets reward-related responses. After phenotype induction, animals were implanted with a monopolar stimulation electrode in the left medial forebrain bundle and trained to press a lever to self-administer electric stimulation of varying frequency. The curve-shift method was used to assess the reward-facilitating effects of d-amphetamine and the reward-attenuating effects of haloperidol (a D(2) antagonist). Thresholds for ICSS were estimated before and after drug/saline injection. The reward-facilitating effects of d-amphetamine were enhanced in quinpirole-treated rats in comparison to controls. This finding suggests that chronic quinpirole-treatment induces changes within the reward circuitry relevant for compulsive behaviour in the rat.
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany. timo.schmidt@mpib-berlin.mpg.de
authors.forename: Timo T
authors.initials: TT
authors.lastname: Schmidt
authors.forename: Ellis
authors.initials: E
authors.lastname: Rea
authors.forename: Julia
authors.initials: J
authors.lastname: Shababi-Klein
authors.forename: George
authors.initials: G
authors.lastname: Panagis
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D003216:Conditioning, Operant / Q000187:drug effects; D003913:Dextroamphetamine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation / Q000009:adverse effects; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D019257:Quinpirole / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012646:Self Administration
chemical_list: D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D019257:Quinpirole; D006220:Haloperidol; D003913:Dextroamphetamine