Role of dopamine systems in obsessive-compulsive disorder (OCD): implications from a novel psychostimulant-induced animal model.
OCD was once considered a rare psychiatric disorder, but recent studies estimate that, in the general population, the lifetime prevalence of OCD is 1 to 2%, twice that of schizophrenia or panic disorder. The most common form of OCD is compulsive checking. Our studies show that the behavior of rats treated chronically with the dopamine agonist, quinpirole, meets the ethological criteria of compulsive checking in OCD; may have a similar motivational basis as compulsive checking in the human; and is partially attenuated by the anti-OCD drug, clomipramine. Thus, the behavioral changes induced by chronic treatment with quinpirole may constitute an animal model of OCD checking. Since behavioral sensitization is an associated effect of quinpirole treatment, the induction of compulsive checking by quinpirole may involve the same mechanisms as the induction of drug-induced sensitization. In this respect, we demonstrated that the MAO inhibitor clorgyline, not only prevented the development of locomotor sensitization to quinpirole, but also reversed it in sensitized rats. To the extent that the quinpirole treatment is an animal model of OCD with strong face validity, it strengthens the hypothesis that dopamine systems play a role in OCD and raises the possibility that MAO inhibitors, which are used clinically for OCD, may exert their effects by acting at the MAO inhibitor displaceable quinpirole binding site.
Szechtman
H
H
Department of Psychiatry and Behavioral Neurosciences, McMaster University, Ontario, Canada.
Culver
K
K
Eilam
D
D
D000818:Animals; D001665:Binding Sites; D002997:Clomipramine / Q000627:therapeutic use; D003010:Clorgyline / Q000494:pharmacology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009771:Obsessive-Compulsive Disorder / Q000209:etiology*; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013997:Time Factors
D002997:Clomipramine; D003010:Clorgyline; D004298:Dopamine; D018491:Dopamine Agonists; D008996:Monoamine Oxidase Inhibitors; D019257:Quinpirole; D017367:Selective Serotonin Reuptake Inhibitors