Evidence for the Modulation of Sexual Behavior by α-Adrenoceptors in Male Rats

Abstract

Clonidine, a commonly used antihypertensive agent believed to act by stimulation of central α- adrenoceptors, produced a dose-related suppression of ejaculatory behavior in sexually vigorous male rats throughout the range of treatment (0.0125–0.5 mg/kg). Treatment with 0.25 mg/kg virtually eliminated ejaculatory behavior, without altering the number of animals mounting and intromitting. These effects were maintained for at least 4 h after treatment. Prazosin, another antihypertensive (but acting by blockade of α₁-adrenoceptors), increased latencies to initiation of copulation, to ejaculation, and to reinstatement of copulation following ejaculation. Additionally, prazosin (1 mg/kg) pretreatment failed to attenuate or prevent the clonidine-induced suppression of ejaculation. In contrast, yohimbine, a drug which preferentially blocks α₂-adrenoceptors (2 mg/kg, 20 min prior to mating tests), caused a facilitation of copulatory behavior as evidenced by drastic decreases in ejaculation latency and intercopulatory and postejaculatory intervals. Pretreatment with yohimbine completely prevented the clonidine-induced suppression of ejaculation, while clonidine attenuated the facilitatory effects of yohimbine, suggesting a competitive interaction. These data lead to the suggestion that increased excitatory adrenergic activity results in increased sexual arousal either by blockade of α₂- or stimulation of α₁-adrenocep-tors. Alternatively, stimulation of α₂- or blockade of α₁-adrenoceptors results in diminished sexual motivation. While the precise implications of this animal research for the clinic are as yet unclear, further research could lead to important developments in the pharmacological treatment of sexual dysfunctions.

Pharmacological analysis of male rat sexual behavior

“…For example, yohimbme (which mcreases NE transmission by blocking inhibitory alpha-2 adrenoceptors) was reported to increase the number of mounts after genital anesthet~zatmn, to increase the percentage of sexually naive males mounting, intromltting and ejaculating, and to decrease the latency to mtromisslon [62]. In another study, yohlmbme faclhtated several copulatory rate and ejaculation threshold measures, including decreased ejaculation latency, postejaculatory interval, mtercopulatory interval, and mtromlssions preceding ejaculation, whde the alpha-2 agonist, clonidine (which decreases noradrenergic transmission), was found to decrease the number of males ejaculating [63] In addition, the alpha-I receptor antagonist, prazosm, slowed copulation by increasing intromission and ejaculation latencies and increasing postejaculatory interval [63]. Finally, a recent report demonstrated that three drugs (yohimblne, imiloxan, and idazoxan) which were found to increase sexual arousal, all bound with high affinity to alpha-2 receptors [130].…”

“…I-DOPA is the precursor molecule for both DA and NE. That the effects of I-DOPA on male copulatory behavior were not due to an increase in noradrenergic neurotransmission was suggested by the observation that the noradrenergic (alpha-2) agonist, clonidine, had little effect on copulatory behavior at doses that did not affect motor capability ( [139], but see [63] discussed below).…”

“…Results from a series of expenments [62,63,130] have suggested that alpha-adrenerg~c receptors specifically affect sexual arousal. For example, yohimbme (which mcreases NE transmission by blocking inhibitory alpha-2 adrenoceptors) was reported to increase the number of mounts after genital anesthet~zatmn, to increase the percentage of sexually naive males mounting, intromltting and ejaculating, and to decrease the latency to mtromisslon [62].…”

Sexual behavior in male rodents

“…A major factor promoting MPOA DA release is (Malmnas, 1976;Mas et al, 1995;Niikura et al, 2002;Rodriguez-Manzo, 1999;Scaletta and Hull, 1990) DA agonists also facilitated copulation in short-term (Malmnas, 1976) and long-term (Scaletta and Hull, 1990) castrated rats. DA antagonists − (Ågmo and Picker, 1990;Ahlenius and Larsson, 1990;Lopez and Ettenberg, 2000, 2002b Noradrenergic NE agonists + (Clark et al, 1984;Clark et al, 1985;Clark, 1995;Rodriguez-Manzo, 1999;Smith et al, 1987;Tallentire et al, 1996) Although noradrenergic drugs appear to facilitate male sexual behavior, high levels of peripheral NE activity inhibit erections (Stefanick et al, 1983) by vasoconstricting penile arteries.…”

Epididymal contraction and sperm parameters are affected by clonidine

“…However, it has been described that the long-term use of clonidine was able to affect the sexual behavior and promotes fertility impairment (Clark et al, 1985;Weiss, 1991). In fact, previous study from our laboratory showed that in vitro treatment with clonidine desensitizes the contractions of rat testicular capsule induced by noradrenaline which could impair the putative transport of spermatozoa from seminiferous tubule to caput of epididymis (Dantas da Silva Junior et al, 2014).…”