title: Performance of compulsive behavior in rats is not a unitary phenomenon - validation of separate functional components in compulsive checking behavior.
abstract: A previous analysis of the quinpirole sensitisation rat model of obsessive-compulsive disorder revealed that the behavioral phenotype of compulsive checking consists of three constitutive components - vigor of checking performance, focus on the task of checking, and satiety following a bout of checking. As confirmation of this analysis, the aim of the present study was to reconstitute, without quinpirole treatment, each of the putative components, with the expectation that these would self-assemble into compulsive checking. To reconstitute vigor and satiety, the employed treatment was a bilateral lesion of the nucleus accumbens core (NAc), as this treatment was shown previously to exaggerate these components. To reconstitute focus, the employed treatment was a low dose of the serotonin-1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin hydrochloride (DPAT) (0.0625 mg/kg), as high doses of this drug induce compulsive behavior and exacerbate focus. Results showed that injection of DPAT to NAc lesion rats did yield compulsive checking. Neither the drug alone nor the NAc lesion by itself produced compulsive checking. The demonstrated synthesis of compulsive checking by the combined treatment of low-dose DPAT and NAc lesion strengthened the previous fractionation of the model obsessive-compulsive disorder phenotype into three constitutive components, and suggested a role for serotonin-1A receptors outside the NAc in enhanced focus on the task of checking.
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, Health Science Centre, McMaster University, Room 4N82, 1280 Main Street West, Hamilton, ON, Canada, L8S 4K1.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Tucci
authors.forename: Anna
authors.initials: A
authors.lastname: Dvorkin-Gheva
authors.forename: Eric
authors.initials: E
authors.lastname: Johnson
authors.forename: Paul
authors.initials: P
authors.lastname: Cheon
authors.forename: Leena
authors.initials: L
authors.lastname: Taji
authors.forename: Arnav
authors.initials: A
authors.lastname: Agarwal
authors.forename: Jane
authors.initials: J
authors.lastname: Foster
authors.forename: Henry
authors.initials: H
authors.lastname: Szechtman
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D003192:Compulsive Behavior / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology*; D009771:Obsessive-Compulsive Disorder; D010641:Phenotype; D020318:Rats, Long-Evans; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology
chemical_list: D058825:Serotonin 5-HT1 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin
keywords: 8-hydroxy-2-(di-n-propylamino) tetralin hydrochloride; analysis and synthesis; animal model; compulsive checking behavior; nucleus accumbens core lesion