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

  • Graf, Marton
  • Kantor, Sandor
  • Anheuer, Zsuzsanna E.
  • Modos, Edit A.
  • Bagdy, Gyorgy

  • Laboratory of Neurochemistry and Experimental Medicine, National Institute of Psychiatry and Neurology, Huvosvolgyi ut 116, Budapest H-1021, Hungary

*Corresponding author. Tel.: +36-1-3915407; fax: +36-1-3915305.

E-mail: [email protected]

Received 10 October, 2002; received in revised form 5 December 2002; accepted 5 December 2002

Behavioural Brain Research 142(1):p 175-179, June 2003. | DOI: 10.1016/S0166-4328(02)00404-7

Abstract

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, 2×50, 2×100 mg/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.

Copyright © 2003Elsevier, Inc.