m-CPP-induced self-grooming is mediated by 5-HT2C receptors

m-Chlorophenylpiperazine (m-CPP), a potent 5-HT receptor agonist, is known to induce self-grooming in rats and exacerbate symptoms in patients with obsessive-compulsive disorder (OCD). To characterise the possible role, 5-HT2B and 5-HT2C receptors play in m-CPP-induced self-grooming, subtype-selective receptor antagonists were used. m-CPP significantly increased the amount of self-grooming in male Sprague-Dawley rats. This effect followed a bell-shaped dose-response curve with a peak at 0.6 mg/kg, i.p. Pretreatment with SB-242084, a subtype-selective 5-HT2C receptor antagonist (0.1-0.5 mg/kg, i.p.), reversed m-CPP-induced self-grooming. In contrast, pretreatment with the subtype-selective 5-HT2B receptor antagonist SB-215505 (1 mg/kg, i.p) did not block the effect of m-CPP. Two days after depletion of brain 5-HT by p-chlorophenylalanine (p-CPA, 2 x 50, 2 x 100mg/kg, i.p.) m-CPP-induced responses were significantly enhanced compared to controls. Our studies provide evidence that direct activation of 5-HT2C receptors mediate m-CPP-induced self-grooming and the depletion of brain 5-HT sensitises these receptors. (C) 2002 Elsevier Science B.V. All rights reserved.