Use of TFMPP stimulus properties as a model of 5-HT1B receptor activation

Recent evidence indicates that when 1-(3-trifluoromethylphenyl)piperazine (TFMPP) is used as a training drug in the drug discrimination paradigm it produces a stimulus effect that is site-selective at the 5-HT1B receptor. The present study sought to employ this procedure in order to assess the similarity of novel agents to TFMPP. First, rats were trained to reliably discriminate between the stimulus properties of intraperitoneally administered 1.0 mg/kg TFMPP and its vehicle. Following the acquisition of this discrimination, administration of various doses of TFMPP produced a typical dose-response relationship with an ED50 of 0.27 mg/kg. Rats were subsequently tested with another 5-HT1B specific agonist 1-(3-chlorophenyl)piperazine (mCPP) and a 5-HT releasing agent norfenfluramine and both produced TFMPP-like discriminative responding in a dose-dependent manner. In contrast, the 5-HT2 agonist 4-iodo-1-(2,5-dimethoxyphenyl)-2-aminopropane (DOI) did not generalize from TFMPP. Other drugs, previously trained in other rats and shown to generalize to TFMPP, viz., ethanol, tetrahydro-beta-carboline (THBC) and 3,4-methylenedioxymethamphetamine (MDMA) did not produce TFMPP-like responding. These results provide further evidence for the 5-HT1B receptor acting as the site for the discriminative effects of TFMPP. In addition, the transfer of discrimination between TFMPP and either ethanol, THBC or MDMA appears to be asymmetrical. Reasons for this one-way generalization are suggested.