Research reportModification of sexual behavior of Long–Evans male rats by drugs acting on the 5-HT1A receptor
Introduction
Drugs that act upon the central nervous system (CNS) are known to modulate sexual behavior in a variety of species 5, 17, 28, 45. Noradrenergic 11, 12and dopaminergic role(s) 25, 42in sexual behaviour are well characterized. The role of the serotonergic system, however, is still controversial [19].
Serotonergic compounds are more difficult to study than adrenergics and dopaminergics because they appear to have an inhibitory effect on sex drive centrally, but an erectogenic effect peripherally. For example, 5-methoxy-N,N-dimethyltryptamine (5-MXDMT, a non-specific 5-HT agonist)[52]was studied for its effects upon penile reflexes in intact and spinal cord transected rats. The authors postulated that the stimulation of serotonin receptors located on autonomic preganglionic or lumbar spinal motor neurons were responsible for ejaculation, followed by suppression of erection. In contrast, DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin), which acts as a specific 5-HT1A agonist in brain [52], and selectively labels the 5-HT1A binding sites [24], was reported to enhance rat copulatory activity primarily by shortening the latency to ejaculation [38]. The results on male sexual behavior is more complex [21]. For example, penile erections are elicited by agents that stimulate 5-HT1B and 5-HT2C receptor sites [10]. In contrast male rat copulatory behavior is inhibited by agents that stimulate 5-HT1B and 5-HT2C[36]or 5-HT2 receptor sites [54], but facilitated by agents that stimulate 5-HT1A receptor sites [33]. Recently, similar results have been found in the rhesus monkey [41].
Sexually dimorphic motor neurons that regulate penile reflexes in the rat have been shown to be located within the anterior horn of the lumbosacral spinal cord [49]. Spinal cord transection studies in rats, and observations in spinal cord injured patients, have demonstrated that penile reflexes are subject to inhibitory supraspinal control [30]. The penile reflexes elicited in the restrained supine rat whose spinal cord is intact, with the penile sheath retracted, are believed to be the counterpart of penile activity during copulation [40].
In this study we report on modulation of both copulatory behavior and penile reflexes elicited in male Long–Evans rats by DPAT, buspirone, and its analog gepirone, as well as BMY-7378 (a proposed 5-HT1A partial agonist). In addition, the interaction of two butyrophenone analogs, spiperone 13, 14, 53(a 5-HT1A and dopamine D2 antagonist) and haloperidol [4](a D2 antagonist) were tested alone and in combination with DPAT.
Section snippets
Animals
Five-month-old male Long–Evans rats (Simonsen Labs, Gilroy, CA; n=96) were used, each weighing between 200–300 g. All rats were fed Purina lab rodent chow, and housed in groups of two. Light was cycled on from 0700 to 1900; temperature and humidity were constant. All 96 rats selected had been shown to respond with reflexes and copulation during three screening procedures. Since the original observations of sexual behavior modifications by DPAT were made on male Sprague–Dawley rats [2], it was
Dose and time-dependent copulatory responses to DPAT, buspirone and gepirone
Five of the six rats treated with saline and all those treated with these drugs displayed full copulatory behavior prior to any drug administration. The time-dependent effects of DPAT (2 mg/kg) upon indices of copulation are shown in Fig. 1. Frequency of intromission (Fig. 1A), length of intromission (Fig. 1B), and latency of ejaculation (Fig. 1C), nadired at approximately 45 min, and normalized either partly or completely by 90 min. This pattern was consistent and it allowed for reassessment
Discussion
Sexual behavior in the male rat involves the activation of two different mechanisms. The first, the arousal mechanism, mediates the initiation and maintenance of sexual excitement. This culminates in a copulatory response, a manifestation of the second aspect. The gain of the arousal mechanism is reflected in the latencies of mounting and intromission. The execution of copulatory and ejaculatory reactions is held to be dependent upon the copulatory mechanism, the gain of which is reflected in
Acknowledgements
The authors thank Dr. Benjamin Sachs for his advice. This work was supported in part by grant GM 34852 from the National Institute of General Medical Sciences.
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2015, Neuroscience and Biobehavioral ReviewsCitation Excerpt :In most cases 5-HT pharmacological manipulation has shown inhibitory effects on sexual motivation and performance (Gorzalka et al., 1990; Zajecka et al., 1991; Hull et al., 2004; Snoeren et al., 2014). The first report that systemic administration of the 5-HT1A receptor agonist 8-hydroxy-2-di-(n-propylamino) tetralin (8-OH-DPAT) reduced the intromission frequency and ejaculation latency was published in 1981 by Sven Ahlenius and Knut Larsson in a collaborative study with the Department of Pharmacology from Gothemburg's University in Sweden (Ahlenius et al., 1981), and this finding has been reproduced many times (Ahlenius and Larsson, 1984; Morali and Larsson, 1984; Mendelson and Gorzalka, 1986; Schnur et al., 1989; Fernández-Guasti and Escalante, 1991; Coolen et al., 1997; Fernández-Guasti and Rodríguez-Manzo, 1997; Rehman et al., 1999; Sura et al., 2001; Snoeren et al., 2014). Although 8-OH-DPAT has some affinity for 5-HT7 receptors (Bard et al., 1993; Neumaier et al., 2001), the findings that systemic injection of other 5-HT1A receptor agonists had similar effects on ejaculation (Fernández-Guasti et al., 1990; Mathes et al., 1990; Ahlenius and Larsson, 1991; Andersson and Larsson, 1994; Haensel and Slob, 1997) and that these effects were completely prevented or reversed by systemic injection of selective 5-HT1A receptor antagonists (Ahlenius et al., 1989; Hillegaart and Ahlenius, 1998) suggested that its facilitatory actions were selectively mediated by the 5-HT1A receptor type (Fernández-Guasti et al., 1990).
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