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mise à jour du
6 mars 2003
Pharmacology Biochemistry & Behavior
1990;35:659-664
lexique
Apomorphine facilitates male sexual behavior
of Rhesus Monkeys
 Steven M. Pomerantz
 Department of Physiology, University of Pittsburgh School of Medicine
 

Chat-logomini

Research with rats suggests that dopaminergic activity may play a role in regulating male sexual behavior. Specifically, drugs which increase dopaminergic activity by stimulating either dopamine synthesis or postsynaptic dopamine receptor sties have been found to facilitate male sexual behavior, whereas drugs that decrease dopaminergic activity by inhibiting either dopamine synthesis or blocking postsynaptic receptor sites have been found to reduce male sexual behavior. Although a great deal is known regarding the mechanism of action of dopamine in regulating male rat sexual behavior, very little is known regarding dopaminergic regulation of male sexual behavior in other species including primates. In studies conducted on rhesus monkeys, administration of the dopamine agonist, apomorphine, did not reliably influence male copulatory performance; however, a reduction of male sexual behavior was observed following administration of the dopamine antagonist, sulpiride.
 
Recently it has been reported that apomorphine stimulated the occurrence of penile erections in both normal and impotent men. Previous studies evaluating the effects of apomorphine on sexual behavior of rhesus monkeys have concentrated on copulatory measures of male sexual behavior and paid little attention to possible effects that these compounds might have on other noncopulatory measures such as penile erection. Therefore, the present study was designed to evaluate the effects of apomorphine on various noncopulatory measures of male sexual behavior. In order to accomplish this aim a novel testing paradigm was developed in which male rhesus monkeys were tested under conditions in which they were exposed to a sexually receptive female that they could see, hear, and smell, but could not physically contact. Under these testing conditions penile erections, courtship behavior, and masturbatory behaviors of male rhesus rnonkeys were able to be evaluated. [...]
 
Discussion
In order to assess neurochemical influences regulating noncopulatory aspects of rhesus male sexual behavior, a novel testing paradigm was developed in which male rhesus monkeys were tested under conditions in which they were exposed to a sexually receptive fernale monkey that they could see, hear, and smeil, but could not physically contact. Under these testing conditions, several measures of male sexual behavior were able to be monitored following drug treatment, including penile erection, courtship behavior, and masturbatory behavior. The present study utilized this paradigm to evaluate the effects of the mixed D1/D2 receptor agonist, apomorphine.
Apomorphine treatment produced a spectrum of behavioral effects that differed depending on the dose of drug administered. Low doses of apomorphine facilitated male sexual responses associated with the genitals, including penile erection and masturbation. These doses also stimulated yawning. At higher doses of apomorphine, sexual responses declined and stereotypic behavior was elicited.
 
Apomorphine has been reported to stimulate both penile erections and yawning in other species including rats and humans. Thus, the finding that rhesus monkeys also respond in a similar fashion to apomorphine administration lends further species generality to the behavioral action of this compound. Since dosages of apomorphine that facilitate penile erections and yawning are substantially lower than dosages that induce stereotypic behavior, it has been widely suggested that apomorphine acts presynaptically on autoreceptors to elicit the former behavioral responses and postsynaptically to elicit the latter behavioral responses.
 
However, a number of studies conducted in rats argue against this hypothesis. First, ( + )-3-PPP, a pre- and postsynaptic dopamine receptor agonist, facilitated penile erections and yawning; whereas, (-)-3-PPP, a presynaptic dopamine receptor agonist and postsynaptic dopamine receptor antagonist failed to influence these behaviors. Secondly, recent studies have demonstrated that direct intracerebral application of apomorphine into the paraventricular nucleus and medial preoptic area facilitated penile erection and yawning. In light of these findings, it has been proposed that the biphasic effects of systemically administered apomorphine on penile erections and yawning may reflect differential stimulation of anatomically separate populations of dopamine receptors. Low doses of apomorphine may preferentially gain access to and stimulate postsynaptic dopaminergic receptors in the medial preoptic area and hypothalamus that facilitate sexual behavior and yawning. At higher dosages, apomorphine may additionally gain access to and stimulate other neural sites (e.g., striatum) that promote behavior stereotypies and interfere with sexual behavior performance.
 
Several studies have addressed whether systemically administered apomorphine is acting centrally or peripherally to affect penile erections. In both rats and humans prior treatment with domperidone, a dopamine antagonist that does not cross the blood-brain barrier, failed to prevent apomorphine from stimulating penile erections. In contrast, treatment with haloperidol or sulpiride, dopamine antagonists that act both centrally and peripherally, blocked penile erections that were induced by systemically administered apomorphine. Similar experiments need to be conducted on rhesus monkeys.
 
Nevertheless, the observation that apomorphine was effective in facilitating penile erections when the stimulus female was present, but not when she was absent, indicates apomorphine may alter sexual behavior by influencing the central processing of sociosexual information. An effect of social testing conditions on apomorphine-stimulated erections has not been reported in studies conducted in rats and humans. However, in the human studies it is important to stress that the subjects were fully aware that they were participating in an erectile response experiment. Therefore, it seems reasonable to postulate that the knowledge of the sexual nature of the experiment may have resulted in some subjects generating sexual images that could potentially influence the ability of apomorphine to facilitate penile erections.
 
Apomorphine significantly stimulated masturbation in the monkeys. Combining the results of both experiments in which 100 µg/kg apomorphine was administered revealed that masturbation occurred in 12 of the 17 tests. In 3 of the 12 tests in which masturbation occurred, the monkeys masturbated to ejaculation. In general, erections were not elicited as a result of masturbatory behavior. Rather, in those tests in which masturbation occurred, the animals began to masturbate only after they achieved at least a grade 2 erection. Thus, it appears that 100 µg/kg apomorphine increased male sexual arousal, resulting in more complete erections and masturbatory behavior which occasionally proceeded to ejaculation. Ejaculations were not observed at other dosages of apomorphine or following vehicle injections. Although there have not been any reports of masturbatory behavior following apomorphine in either rats or humans, apomorphine has been found to stimulate seminal emission in rats.
 
Apomorphine treatment failed to significantly stimulate male courtship behavior of the monkeys. This finding is in marked contrast to the capacity of apomorphine to potentiate other measures of male sexual arousal such as penile erection and masturbation. Although different sexual behaviors may be differentially sensitive to dopaminergic stimulation, it is possible that the testing conditions being utilized did not provide an environment in which a significant drug effect on courtship behaviors could emerge. Since courtship purse-lip gestures in macaque species generally serve as an affiliative signal produced while males are at a distance from the female, the close proximity of the stimulus female to the male in the present studies may have reduced the need for the male to exhibit these behaviors. Thus, male courtship performance may have reached an asymptote under vehicle conditions. Further testing will have to evaluate this possibility by determining whether courtship behaviors are affected by increasing the distance between the experimental male and stimulus female.
 
High dosages of apomorphine elicited excessive gnawing, licking and fingering of a metal clip attached to the cage. This finding replicates similar reports of high doses of apomorphine producing oral hyperkinesia in several different nonhuman primate species including rhesus rnonkeys. These other studies did not evaluate the effects of these dosages of apomorphine on sexual phenomena or yawning; however, in the present study, dosages of apomorphine that produced oral hyperkinesia also led to a decline in penile erections and yawning. Although the biphasic effect of apomorphine on penile erection may be a result of behavioral stereotypies interfering with sexual effects of this compound, recent data in the rat have demonstrated that apomorphine administered directly into the lumbosacral subarachnoid space inhibited penile reflexes. This finding suggests that apomorphine may have contrasting effects on behavior depending on its ability to gain access te, different neural sites at which dopamine acts to promote or inhibit sexual behavior.

« It is ironic that testosterone "the male sex hormone," is more closely associated with the yawning rate than with the mounting or intromitting rates » Charles Phoenix
 
 
Sexual steroids exert several effects on both central dopaminergic and oxytocinergic systems by acting either at the genomic or membrane level  
yawns-canines
credit photo : "Asif A. Ghazanfar and Aristides Arrenberg"
Max Planck Institute for Biological Cybernetics
Tuebingen; Germany.
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