Selective alleviation of compulsive lever-pressing in rats by D1, but not D2, blockade: Possible implications for theinvolvement of d receptors in obsessive-compulsivedisorder

Abstract

Rats undergoing extinction of lever-pressing for food after the attenuation of an externalfeedback for this behavior exhibit excessive lever-pressing unaccompanied by an attempt to collect a reward. This behavior may be analogous to the excessive and unreasonablebehavior seen in obsessive-compulsive disorder. In the present study, we tested the hypothesis that the compulsive behavior induced bysignalattenuation is mediated via D1 ratherthan D2 receptors. Administration of 0.005, 0.01 and 0.03 mg/kg ofthe D1 antagonist SCH23390 reduced the number of compulsive lever-presses without affecting the number of lever-presses followed by an attempt to collecta reward. In contrast, administration of 0.005, 0.01,0.024, 0.036 and 0.05 of the D2antagonist haloperidoldose-dependently decreasedboth types of lever-presses. In addition, haloperidolat doses that decreased lever-pressing in the post-training signalattenuationprocedure (0.036 and 0.05 mg/kg) had a similar effect in regular extinction, whereas an SCH 23390 dose that decreased compulsivelever-pressing in the post-training signalattenuation procedure (0.01 mg/kg) had no effect on regular extinction. On the basis ofelectrophysiologicaldata on the response of dopamine neurons to the omission of an expected reward, these results were interpreted assuggesting that compulsive lever-pressing depends on a phasic decrease in the stimulation of D receptors. The implications of theseresults for the pathophysiology and treatment of obsessive-compulsive disorder are discussed. © 2003 American College of Neuropsychopharmacology.