Extracellular serotonin in the lateral hypothalamic area is increased during the postejaculatory interval and impairs copulation in male rats

Abstract

Serotonin (5-HT) is generally inhibitory to masculine sexual behavior. It has been suggested that 5-HT released after ejaculation may promote the sexual quiescence of the postejaculatory interval (PEI). The following experiments were conducted to test (1) whether extracellular 5-HT increases in either the anterior lateral hypothalamic area (LHAA) or the medial preoptic area (MPOA) of male rats after ejaculation; (2) whether increasing 5-HT in these sites, by microinjecting the selective serotonin reuptake inhibitor alaproclate, could inhibit copulatory abilities; and (3) whether copulation deficits produced by alaproclate were attributable to locomotor impairments. The effects of local application of alaproclate on extracellular 5-HT levels in the LHAA and the MPOA were also tested. Extracellular serotonin was measured in all experiments using in vivo microdialysis. Ejaculation was correlated with enhanced 5-HT release from the LHAA; no 5-HT increases were observed before ejaculation, and levels were decreased toward basal values during a subsequent copulatory series. Elevating 5-HT in the LHAA by microinjecting alaproclate inhibited copulation by increasing the latency to mount, intromit, and ejaculate. This inhibition did not result from nonspecific locomotor impairments. In the MPOA, 5-HT release remained stable throughout copulation, and microinjecting alaproclate into this site did not significantly alter sexual behavior. These data support the large body of evidence suggesting that 5-HT is inhibitory to masculine sexual behavior. Furthermore, the LHAA, but not the MPOA, may be one site responsible for serotonergic inhibition of copulation during the PEI.

Fig. 1.

Chromatogram showing a dialysate sample from the LHA_A (bottom trace) and a mixture of standards (top trace) for (1) dihydroxyphenylacetic acid (DOPAC), (2) 5-HIAA, (3) homovanillic acid (HVA), (4) 3-methoxytyramine (3-MT), and (5) 5-HT. The concentrations of the standards were 4 pg/μl (2 pg/0.5 μl injected onto the column).

Fig. 2.

Temporal changes in dialysate concentrations of serotonin (5-HT) collected from the LHA_A of seven subjects during copulatory activities. Each data point represents the mean ± SE for 6 min samples collected during baseline (B), in the presence of an estrous female (F), during copulation (C), during the postejaculatory interval (P), and after the female was removed (expressed as a percentage of baseline 5-HT levels). Four samples were analyzed after removal of the female at 30 min intervals. Serotonin levels were increased during the second (P2) and third (P3) PEI; *p < 0.05 versus final baseline (B), female behind barrier (F), and the first active copulation series (C1). Levels during the third PEI were also significantly greater compared with series 4 active copulation (C4). Samples collected during the second and third copulation series were not analyzed, because most animals ejaculated before a full 6 min sample could be collected. The summary graph (inset) represents the mean ± SE for data from the 15 sample periods collapsed into five groups, based on behavioral condition. Samples collected during PEIs (P) show enhanced 5-HT concentrations; *p < 0.05 versus B, F, C, and postcopulation (POST). Basal extracellular concentrations in the LHA_A were estimated to be 1.6 ± 0.1 nm.

Fig. 3.

Temporal changes in dialysate concentrations of 5-HT collected from the MPOA of 16 subjects during copulatory activities. One sample was collected 30 min after removal of the female. Each data point represents the mean ± SE from 6 min sampling intervals. No change in 5-HT release was observed during the sampling periods. Basal extracellular concentrations of 5-HT in the MPOA are estimated to be 1.4 ± 0.1 nm.

Fig. 4.

Mean ± SE for locomotor activities after 0.0 or 20.0 μg of bilateral alaproclate microinjections into the LHA_A of 12 subjects. Six subjects received the low dose, and a separate group of six subjects received the high dose. There was no change in the number of lines crossed (A) or the number of rearings (B). The time spent grooming (C) increased during the 12 min test session after 20.0 μg of alaproclate microinjection; *p< 0.05 versus 0.0 μg.