A discriminative stimulus produced by 1-(3-chlorophenyl)-piperazine (mCPP) as a putative animal model of anxiety

1. This study compares behavioral responses to serotonergic (5HT) agonists and pentylenetetrazol (PTZ) in two behavioral paradigms used as animal models of anxiety. PTZ and mCPP were compared for behavioral effects in elevated plus-maze and interoceptive discriminative stimuli they produce. 2. PTZ is a known anxiogenic drug. The discriminative stimuli of mCPP were selected for comparison because this drug produces "anxiety" in human subjects and "anxiety-like" behaviors in rats, and is a potent agonist at 5HT1B/2C receptors and a partial agonist at 5HT2A receptors. 3. In rats trained to discriminate mCPP (1.4 mg/kg, training dose) from saline, PTZ substituted for the mCPP suggesting the "anxiety-like" properties of the mCPP stimulus. The mCPP stimulus was blocked in a dose-related manner by methysergide, a 5HT2A/2C antagonist but not by the anxiolytic diazepam. TFMPP (a 5HT agonist) and DOI (a 5HT2A/2C agonist) substituted for mCPP, but 1-NP (a 5HT1 agonist and 5HT2C/2A antagonist) did not. 4. In animals trained to discriminate PTZ (16 mg/kg) from saline, mCPP and DOI substituted for PTZ, while TFMPP and 1-NP do not. 5. In the elevated plus maze, time spent on the open arms was reduced by mCPP, DOI and PTZ but there was no significant dose effect of TFMPP, or 1-NP. 6. Methysergide blocked the "anxiety-like" behavior in the EPM. 7. These data suggest that the discriminative stimuli produced by mCPP are based upon its selective actions on 5HT receptors and their use in behavioral pharmacology may offer another tool in studying pharmacology of 5HT based anxiogenic and anxiolytic drugs.