Department of
Physiology, University of Pittsburgh School of
Medicine
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
