Discriminative stimulus properties of the serotonergic compound eltoprazine

The 5-hydroxytryptamine-1a/1b (5-HT1a/1b) agonist eltoprazine is the main representative of the so-called "serenics," a group of drugs sharing a specific antiaggressive activity. Rats were trained to discriminate an i.p. dose of 0.5 mg/kg of eltoprazine from saline in a two-lever operant drug discrimination task using a fixed ratio 10 schedule of food reinforcement. The cue of eltoprazine was found to be dose and time dependent. The eltoprazine stimulus generalized to the structurally related experimental drug fluprazine, the mixed 5-HT1a/1b agonist 5-methoxy-3-(1,2,3,6-tetrahydropyridinyl)-1H indole, (RU 24969), the 5-HT1b/1c agonist 1-[3-(trifluoromethyl)phenyl]piperazine, (TFMPP), the 5-HT1a agonist 8-hydroxy-2-(di-n-propylamino)tetralin-HB, (8-OH-DPAT), and the beta adrenergic/5-HT1 antagonists (+/-)-pindolol and (+/-)-propranolol. The eltoprazine cue partially generalized to the cues of the 5-HT1a agonists flesinoxan and buspirone, (m-CPP), the 5-HT1b/1c agonist 1,3-chlorophenyl-piperazine dihydrochloride and the 5-HT1c/2 antagonist mesulergine, and did not generalize to the 5-HT2/1c agonist DOI. During tests of antagonism, neither mesulergine, the nonspecific 5-HT antagonist methysergide, the 5-HT2 antagonist ketanserin, the 5-HT3 antagonist tropisetron (ICS 205-930), nor (+/-)-pindolol and (+/-)-propranolol attenuated the stimulus effect of eltoprazine. The specific beta adrenergic antagonist timolol did not substitute for eltoprazine. The present data show that eltoprazine can serve as a discriminative stimulus in rats and suggest that specifically 5-HT1 (i.e., 5-HT1a and 5-HT1b) receptors are involved in the stimulus properties of eltoprazine.(ABSTRACT TRUNCATED AT 250 WORDS)