Evidence that mCPP-induced anxiety in the plus-maze is mediated by postsynaptic 5-HT2C receptors but not by sympathomimetic effects.
1-(3-Chlorophenyl)piperazine (mCPP) (0.125-1.0 mg/kg i.p.), previously shown to inhibit social interaction, dose-dependently reduced exploration of the open arms of an elevated plus-maze. These findings suggest anxiogenic properties. The effect of mCPP was more potently inhibited by 1-(1-naphthyl)piperazine than by ketanserin, indicative of its mediation via activation of 5-HT2C rather than 5-HT2A receptors. The 5-HT1B receptor agonist CGS 12066B did not antagonise the anxiety-like response to mCPP, and further reduced exploration at the highest dose tested (10 mg/kg i.p.). Depletion of serotonin (5-HT) by p-chlorophenylalanine (PCPA, 150 mg/kg/day x 3) did not prevent the response, although PCPA itself increased open arm exploration. The 5-HT1A/B and beta-adrenoceptor antagonist 1-propanolol (5 mg/kg i.p.) and the peripheral beta 1-receptor antagonist atenolol (20 mg/kg i.p.) showed no significant activity on the plus-maze either alone or against the anxiogenic effect of mCPP. These results indicate that mCPP induces anxiety in the rat in the elevated plus-maze primarily by stimulation of postsynaptic 5-HT2C receptors, and suggest that sympathomimetic effects of mCPP are not involved.
Gibson
E L
EL
Department of Neurochemistry, Institute of Neurology, London, U.K.
Barnfield
A M
AM
Curzon
G
G
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013566:Sympathomimetics / Q000494:pharmacology*; D013569:Synapses / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D010879:Piperazines; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D013566:Sympathomimetics; C048241:1-(1-naphthyl)piperazine; D010134:Fenclonine; C015068:1-(3-chlorophenyl)piperazine