Partial antagonism of 8-OH-DPAT'S effects on male rat sexual behavior with a D2, but not a 5-HT1A, antagonist.

The serotonin agonist 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), injected systemically or directly into the medial preoptic area (MPOA), reduces the ejaculatory threshold in male rats. While 8-OH-DPAT has been characterized as an agonist at the 5-HT1A receptor, it also acts at other receptor sites including the dopamine D2 receptor. The current experiments investigated whether 8-OH-DPAT injected into the MPOA facilitates male sexual behavior through stimulation of the 5-HT1A receptor or the dopamine D2 receptor. Experiment 1 co-administered 8-OH-DPAT (6 microgram) with either the 5-HT1A antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-ben zamide hydrochloride (MPPI) (10 microgram) or the D2 antagonist raclopride (10 microgram). Raclopride blocked 8-OH-DPAT's facilitative effects on ejaculation frequency and latency, while the 5-HT1A antagonist was ineffective. In Experiment 2, 8-OH-DPAT (500 microM), retrodialyzed into the MPOA through a microdialysis probe, enhanced male copulatory behavior similarly to the microinjection, increasing ejaculation frequency and decreasing ejaculation latency, postejaculatory interval and mount frequency. Retrodialyzing 8-OH-DPAT through a microdialysis probe in the MPOA had been previously shown to increase extracellular levels of dopamine and serotonin. The data from the present studies suggest that the effects of 8-OH-DPAT in the MPOA on male rat copulatory behavior may be mediated, at least in part, either directly through 8-OH-DPAT's activity at D2 receptors or indirectly through 8-OH-DPAT's ability to increase extracellular dopamine. Copyright 1999 Elsevier Science B.V.