Rapid discrimination of the stimulus properties of 5-hydroxytryptamine agonists using conditioned taste aversion

Separate groups of rats were trained to discriminate the stimulus properties of selective agonists at 5-HT receptors using a conditioned taste aversion procedure. Fluid-restricted rats were injected with drug or saline and then given access to a 0.25% saccharin solution for 30 min. When rats received a drug trial, saccharin consumption was followed by an injection of LiCl (1.8 mEq/kg i.p.), whereas on saline trials saccharin consumption was followed by a second injection of saline instead of LiCl. Rats were trained using injections of either 8-hydroxy-2-(di-n-propylamino)tetralin (0.4 mg/kg i.p.), an agonist selective for the 5-HT1A receptor, or 1-(m-trifluoromethylphenyl)piperazine (0.8 mg/kg i.p.), an agonist selective for 5-HT1B and 5-HT1C receptors, as the drug stimuli. Acquisition of the discriminated taste aversion, as measured by the differential effects on saccharin drinking between drug and saline trials, required only two to three pairings of either drug stimulus with LiCl injections. The 8-hydroxy-2-(di-n-propylamino)tetralin discriminative stimulus cue generalized to other drugs that are selective for the 5-HT1A receptor, such as ipsapirone (8-16 mg/kg i.p.) or buspirone (4 mg/kg i.p.), but not to agonists that are selective for the 5-HT1B/1C receptor, such as 1-(m-trifluoromethylphenyl)piperazine or 1-(m-chlorophenyl)piperazine. The discriminative stimulus properties of 1-(m-trifluoromethylphenyl)piperazine generalized to 1-(m-chlorophenyl)piperazine (0.2-0.8 mg/kg i.p.) but not to the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (0.4 mg/kg i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)