8-OH-DPAT influences extracellular levels of serotonin and dopamine in the medial preoptic area of male rats.

Serotonin (5-HT) is generally inhibitory to male rat sexual behavior. However, the 5-HT1A agonist 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), injected either systemically or into the medial preoptic area (MPOA), facilitates ejaculation. Three experiments were conducted to test the effects of 8-OH-DPAT on 5-HT and dopamine (DA) neurotransmission in the MPOA, a very important site for the control of male sexual behavior. In Experiment 1, systemically injected 8-OH-DPAT (0.4 mg/kg) decreased extracellular 5-HT levels in the MPOA as measured by in vivo microdialysis. In Experiment 2, 8-OH-DPAT (500 microM) administered directly into the MPOA via reverse dialysis increased extracellular levels of both DA and 5-HT; pretreatment with the selective 5-HT1A antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-ben benzamide hydrochloride (p-MPPI) failed to prevent 8-OH-DPAT's stimulatory effects on DA and 5-HT levels in the MPOA. In Experiment 3, 8-OH-DPAT (8 microg) co-injected with 5,7-dihydroxytryptamine (5,7-DHT; 6 microg) prevented neurotoxic depletion of 5-HT in the site of injection (MPOA). Because systemic and MPOA injections of 8-OH-DPAT resulted in opposite effects on extracellular 5-HT in the MPOA, yet both can facilitate ejaculation, these data suggest that moderate changes in 5-HT in the MPOA may have relatively little influence on male copulatory behavior. Instead, the facilitative effects of 8-OH-DPAT in the MPOA on male copulatory behavior may result, at least in part, from stimulatory effects of 8-OH-DPAT on DA transmission. Facilitative effects of systemic injections of 8-OH-DPAT may result from decreased 5-HT release in several sites.