INVOLVEMENT OF 5-HT2C RECEPTORS IN MEDIATING THE DISCRIMINATIVE STIMULUS PROPERTIES OF M-CHLOROPHENYLPIPERAZINE (MCPP)

Rats were trained to discriminate the 5-HT receptor agonist m-chloroph enylpiperazine (mCPP; 1 mg/kg) from saline using a two-lever, water-re inforced drug discrimination task. The antidepressant trazodone (1-8 m g/kg), the 5-HT1B/2C receptor agonists 1-(m-trifluoromethylphenyl)pipe razine (TFMPP; 0.25-1 mg/kg) and MK 212 (0.125-1 mg/kg), and the mixed 5-HT1A/B receptor agonist RU 24969 (0.25-2 mg/kg) substituted fully f or mCPP. The 5-HT2A/2C receptor agonists 1-(2,5-dimethoxy-4-iodophenyl )-2-aminopropane (DOI; 0.25-1 mg/kg) and d-lysergic acid diethylamide (LSD; 0.02-0.08 mg/kg) and the 5-HT releaser fenfluramine (0.5-2 mg/kg ) also mimicked mCPP. Agonists selective for the 5-HT1A or 5-HT3 recep tor or the 5-HT reuptake site produced saline-lever responding. The er goline derivative mesulergine (0.5-4 mg/kg) produced a partial agonist /antagonist profile. The 5-HT1/2 receptor antagonist metergoline (0.12 5-1 mg/kg) completely blocked the mCPP cue whereas the 5-HT2A/2C recep tor antagonists ketanserin and LY 53857 as well as all other 5-HT rece ptor antagonists failed to block the mCPP cue. The dopamine receptor a ntagonists SCH 23390 and haloperidol were also ineffective mCPP antago nists, Following pretreatment with the 5-HT synthesis inhibitor p-chlo rophenylalanine (pCPA; 100 mg/kg/day) for 3 consecutive days, the disc riminability of low doses of mCPP increased, whereas the effects of fe nfluramine decreased. The present results suggest that the discriminat ive stimulus effects of mCPP in rats are mediated primarily by postsyn aptic 5-HT2C receptors.