Selective alleviation of compulsive lever-pressing in rats by D1, but not D2, blockade: possible implications for the involvement of D1 receptors in obsessive-compulsive disorder.
Rats undergoing extinction of lever-pressing for food after the attenuation of an external feedback for this behavior exhibit excessive lever-pressing unaccompanied by an attempt to collect a reward. This behavior may be analogous to the excessive and unreasonable behavior seen in obsessive-compulsive disorder. In the present study, we tested the hypothesis that the compulsive behavior induced by signal attenuation is mediated via D(1) rather than D(2) receptors. Administration of 0.005, 0.01 and 0.03 mg/kg of the D(1) antagonist SCH 23390 reduced the number of compulsive lever-presses without affecting the number of lever-presses followed by an attempt to collect a reward. In contrast, administration of 0.005, 0.01, 0.024, 0.036 and 0.05 of the D(2) antagonist haloperidol dose-dependently decreased both types of lever-presses. In addition, haloperidol at doses that decreased lever-pressing in the post-training signal attenuation procedure (0.036 and 0.05 mg/kg) had a similar effect in regular extinction, whereas an SCH 23390 dose that decreased compulsive lever-pressing in the post-training signal attenuation procedure (0.01 mg/kg) had no effect on regular extinction. On the basis of electrophysiological data on the response of dopamine neurons to the omission of an expected reward, these results were interpreted as suggesting that compulsive lever-pressing depends on a phasic decrease in the stimulation of D(1) receptors. The implications of these results for the pathophysiology and treatment of obsessive-compulsive disorder are discussed.
Joel
Daphna
D
Department of Psychology, Tel Aviv University, Romat-Aviv, Israel. djoel@post.tau.ac.il
Doljansky
Julia
J
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003192:Compulsive Behavior / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D006234:Handling, Psychological; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000523:psychology*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012201:Reward; D017603:Signal Detection, Psychological / Q000187:drug effects
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D006220:Haloperidol