Discriminated taste aversion with a 5-HT agonist measured using saccharin preference

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Rats were trained to discriminate the stimulus properties of the selective 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.4mg/kg i.p.) versus saline, using a discriminated taste aversion procedure. Tests of stimulus generalization and drug substitution were conducted using two-bottle choice tests between saccharin and water. Rats that received pairings of 8-OH-DPAT with LiCl demonstrated significant reductions of saccharin preference when administered 8-OH-DPAT at doses of 0.1mg/kg or higher. 8-OH-DPAT did not alter saccharin preference significantly in controls that did not receive LiCl injections. Other drugs with high affinity for 5-HT(1A) receptors, such as the azapirones gepirone, ipsapirone and buspirone, produced selective reductions of saccharin preference in rats trained to discriminate 8-OH-DPAT from saline but not in controls. Three drugs with low affinity for 5-HT(1A) receptors, the benzodiazepine anxiolytic diazepam, d-amphetamine, and a common metabolite of the azapirones 1-(2-pyrimidinyl) piperazine (1-PP) altered fluid intake significantly but failed to produce significant changes in saccharin preference in either the discrimination or control groups. This study indicates that two-bottle preference tests can be used to measure the stimulus properties of 8-OH-DPAT trained using a discriminated taste aversion procedure, because the stimulus effects of drugs, measured using saccharin preference, can be separated from the nonspecific effects of drugs on fluid consumption.