Discriminative stimulus properties of indorenate, a serotonin agonist

Objective: To determine whether indorenate, a serotonin-receptor agonist, c an exert discriminative control over operant responses, to establish the te mporal course of discriminative control and to compare its stimulus propert ies to a (5-HT)(1A) receptor agonist, [H-3]-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT). Design: Prospective animal study. Animals: Ten male W istar rats. Interventions: Rats were trained to press either of 2 levers fo r sucrose solution according to a fixed ratio schedule, which was gradually increased. Rats were given injections of either indorenate or saline solut ion during discrimination training. Once they had achieved an 83% accuracy rare, rats underwent generalization tests after having received a different dose of indorenate, the training dose of indorenate at various intervals b efore the test, various doses of 8-OH-DPT, or NAN-190 administered before i ndorenate or 8-OH-DPAT Outcome measures: Distribution of responses between the 2 levers before the first reinforcer of the session, response rate for all the responses in the session, and a discrimination index that expressed the drug-appropriate responses as a proportion of the total responses. Res ults: indorenate administration resulted in discriminative control over ope rant responses, maintained at fixed ratio 10, at a dose of 10.0 mg/kg (but not 3.0 mg/kg). When the interval between the administration of indorenate and the start of the session was varied, the time course of its cue propert ies followed that of its described effects on 5-HT turnover. In generalizat ion tests, the discrimination index was a function of the dose of indorenat e employed; moreover, administration of 8-OH-DPAT (from 0.1 to 1.0 mg/kg) f ully mimicked the stimulus properties of indorenate in a dose-dependent way . The (5-HT)(1A) antagonist NAN-190 prevented the stimulus generalization f rom indorenate to 8-OH-DPAT. Also, NAN-190 antagonized the stimulus control of indorenate when administered 45 minutes before the session, but not whe n administered 105 minutes before the session (i.e. 15 minutes before the a dministration of indorenate). Conclusion: (5-HT)(1A) receptors are of relev ance to the stimulus function of indorenate. However, other receptor subtyp es may also be involved. Hence, other agonists and specific antagonists sho uld be studied before definite conclusions are drawn.