Interactions between serotonergic agonists and antagonists in rats trained with LSD as a discriminative stimulus

Drugs purported to have selective affinities for 5-HT_1A, 5-HT_1B, and 5-HT₂ receptors were tested in rats trained with 0.1 mg LSD versus saline. Included were 5-methoxy-dimethyltryptamine (MDMT), 2,5-dimethoxy-4-methyl-amphetamine (DOM), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), m-trifluoromethylphenyl-piperazine (TFMPP), and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU-24969). Tests were then repeated in the presence of either pizotyline or pirenperone. DOM substituted for LSD and both were blocked by pizotyline and pirenperone. MDMT, 8-OH-DPAT, TFMPP, and RU-24969 substituted less completely and were variably affected by the antagonists. An unexpected result was potentiation of the stimulus or disruptive effects of certain doses of 8-OH-DPAT and TFMPP by pizotyline and pirenperone. The present findings suggest more complex interactions between these drugs than has previously been assumed.