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-HT(2B) and 5-HT(2C) 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-HT(2C) receptor antagonist (0.1-0.5 mg/kg, i.p.), reversed m-CPP-induced self-grooming. In contrast, pretreatment with the subtype-selective 5-HT(2B) 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 100 mg/kg, i.p.) m-CPP-induced responses were significantly enhanced compared to controls. Our studies provide evidence that direct activation of 5-HT(2C) receptors mediate m-CPP-induced self-grooming and the depletion of brain 5-HT sensitizes these receptors.
Graf
Marton
M
Laboratory of Neurochemistry and Experimental Medicine, National Institute of Psychiatry and Neurology, Huvosvolgyi ut 116, Budapest H-1021, Hungary.
Kantor
Sandor
S
Anheuer
Zsuzsanna E
ZE
Modos
Edit A
EA
Bagdy
Gyorgy
G
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D006120:Grooming / Q000187:drug effects* / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D010879:Piperazines; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C112812:serotonin 1C receptor; C015068:1-(3-chlorophenyl)piperazine