DIFFERENTIATION OF 5-HT1A RECEPTOR LIGANDS BY DRUG DISCRIMINATION

Pigeons were trained to discriminate 0.64 mg/kg (high dose) of 8-OH-DP AT (8-hydroxy-(2-di-n-propylamino)tetralin) from saline or were retrai ned to discriminate 0.16 mg/kg (low dose) of 8-OH-DPAT from saline. Th is resulted in a decrease of the ED50 for recognition of the 8-OH-DPAT cue from 0.14 to 0.04 mg/kg. Partial agonists for the 5-HT1A receptor (e.g., buspirone) were generalized fully in the low dose condition, bu t only partially in the high dose condition. Full antagonists, such as N-{2-[4-(2-methoxyphenyl)-1- zinyl]ethyl}-N-(2-pyridinyl)cyclohexanec arboxamide (WAY-100635), antagonized the 8-OH-DPAT cue in both groups without producing generalization in either group. (-)-Pindolol produce d full generalization in the low dose group, but antagonized the high dose stimulus cue. The behavioral effects of other compounds with 5-HT 1A receptor activities phenyl)-1-piperazinyl]ethyl]-N-pyridinyl-benzam ide hydrochloride (p-MPPI); -(1H-indol-4-yloxy)-3-(cyclohexylamimo)-2- propanol maleate ((-)-LY206130); racemic pindolol and idazoxan) also d iffered between groups. Comparing results obtained using differing tra ining doses in the drug discrimination paradigm simplifies determinati on of the full agonist, partial agonist, or antagonist properties of c ompounds. (C) 1997 Elsevier Science B.V.