Discriminated taste aversion with a 5-HT(1A) agonist measured using saccharin preference.
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.
Departments of Psychiatry and Pharmacology, University of Pennsylvania, 207 Piersol Building, Philadelphia, PA 19104-4283 USA.
I.
I
Lucki
J.M.
JM
Marcoccia