title: 5-HT2A/C receptors do not mediate the attenuation of compulsive checking by mCPP in the quinpirole sensitization rat model of obsessive-compulsive disorder (OCD).
abstract: There is emerging evidence for a dopamine (DA)-serotonin (5-HT) interaction underlying obsessive-compulsive disorder (OCD). In the quinpirole sensitization rat model of OCD, compulsive checking is induced by chronic treatment with the DA agonist quinpirole, and is attenuated by the 5-HT agonist drug mCPP. However, mCPP has affinity for a number of 5-HT receptor subtypes, and it is unknown by which receptors mCPP exerts its effects on quinpirole-treated animals. The present study tested in rats whether mCPP activity at 5-HT2A/C receptors mediates the attenuation of compulsive checking in quinpirole-treated animals. Rats were chronically treated with quinpirole on the open field for the induction of compulsive checking. Following the induction phase, animals were treated with mCPP (1.25 mg/kg) and the selective 5-HT2A/C receptor antagonist ritanserin (1 mg/kg or 5 mg/kg) to test whether blockade of 5-HT2A/C receptors inhibits attenuation of checking by mCPP. Results showed that as expected, quinpirole induced compulsive checking, and mCPP reduced its performance. However, 5-HT2A/C receptor blockade by ritanserin did not inhibit the attenuation of compulsive checking by mCPP. These results suggest that the reduction in compulsive checking by mCPP is not mediated by activity at 5-HT2A/C receptors, but by another receptor subtype.
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, HSC, 4N7, 1280 Main Street West, Hamilton, ON, Canada L8S4L8. Electronic address: markctucci@gmail.com.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Tucci
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, HSC, 4N7, 1280 Main Street West, Hamilton, ON, Canada L8S4L8.
authors.forename: Anna
authors.initials: A
authors.lastname: Dvorkin-Gheva
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, HSC, 4N7, 1280 Main Street West, Hamilton, ON, Canada L8S4L8.
authors.forename: Eric
authors.initials: E
authors.lastname: Johnson
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, HSC, 4N7, 1280 Main Street West, Hamilton, ON, Canada L8S4L8.
authors.forename: Michael
authors.initials: M
authors.lastname: Wong
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, HSC, 4N7, 1280 Main Street West, Hamilton, ON, Canada L8S4L8.
authors.forename: Henry
authors.initials: H
authors.lastname: Szechtman
mesh_terms: D000818:Animals; D003192:Compulsive Behavior / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000139:chemically induced / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D020318:Rats, Long-Evans; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D016713:Ritanserin / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; D019257:Quinpirole; C015068:1-(3-chlorophenyl)piperazine
keywords: 5-HT2A/C; Animal model; Obsessive–compulsive disorder (OCD); Quinpirole; Ritanserin; mCPP