Several neurotransmitters and neuropetides
are involved at the level of the paraventricular
nucleus of the hypothalamus (PVN) in the control
of yawning and penil erection that occurs in
ex-copula and in-copula conditions. Accordling,
oxytocin, D2 dopamine receptor agonists and NMDA
induce penile erection and yawning when injected
into the PVN of freely moving rats. Also, D2
receptor agonists injected into the PVN modulate
genital reflexes in restrained male rats and
during copulation. The behavioural effects
observed after injection of D2 receptors
agonists NMDA and oxytocininto the PVN may be
secondary to the activation of a group of
oxytocinergic neurons that originate in the PVN
and project to extrahypothlamic brain areas,
and/or, as far as for penile erection is
cocerned, to the spinal lumbosacral nucleus of
the bulbospongiosum and to the penis. The
facilitative effects of dopamine receptor
agonists. NMDA and oxytocin on penile erection
and yawning are apparently mediated by an
increased production of nitric oxide (NO) in the
cell bodies of these oxytocinergic neurons.
Accordingly, NO donors injected into the PVN
induce penile erections and yawns, that are
indistinguishable from those induced by the
above compounds, by activating central
oxytocinergic transmission. Finaly dopamine
receptor agonist, oxytocin and NMDA induce
penile erection and the concomitant increase in
NO production in the PVN can be prevented by the
opiate morphine injected into the PVN in a
naloxone-dependent manner.
Mechanisms similar to those described above
seem to operate in the PVN when penile erection
occurs in physiological contexts., eg during non
contact erections and copulation. Noncontact
erections and steroid dependenterections,
mediated by volatile pheromones, which occur
sexually potent mal rats exposed to an
inaccessible receptive female, and are
considered a model for investigating the neural
mediatin of sexual arousal. several lines of
experimental evidence support this hypothesis.
First vasotencin, given into lateral ventricles,
not only prevents drug and oxytocin-induced
penile erection, but also prevents noncontact
and impairs copulation. Second, NO production is
increased in the PVN during noncontact erections
and copulation and this increase is prevented by
the NO synthase inhibitor nitro-L-arginine
methylester, by morphine or by the NMDA receptor
antagonist. MK-801, injected into the PVN at
doses that also prevent noncontact erections and
copulation.
We have recently found that the activation of
GABAA receptors, by Muscirnol, in the PVN
prevents both penile erection and yawning
induced by the mixed D1/D2, receptor agonist,
apomorphine, and by oxytocin and NMDA and also
noncontact penile erections. These findings are
in line with immunocytochemical and
electrophysiological studies showing that
paraventricular magnocellular and parvocellular
oxytocinergic neurons are under inhibitory
GABAergic control and suggest that GABA is also
involved at the PVN level in the control of
penile erection and yawning. Accordingly,
GABA synapses impinge on the cell bodies of
oxytocinergic neurons, and GABA agonists
decrease oxytocinergic transmission in several
circumstances. The majority of these inhibitory
synapses belong to GABAergic neurons originating
mainly in the perinuclear region that surrounds
the PVN, although the presence of
intraparaventricular GABAergic neurons cannot be
ruled out. To further characterize the role
of GABA, at the level of the PVN, in the control
of yawning and penile erection, we studied
the effect of muscimol on the increase of
paraventricular NO production that occurs
concomitantly with penile erection and yawning
induced by apornorphine, oxytocin and NMDA as
well as during noncontact penile erections.
[...]
Discussion
The present results confirm and extend
previous studies showing that muscimol, a GABAa
receptor agonist, but not baclofen, a GABAb
receptor agonist, delivered into the PVN reduces
penile erection and yawning induced by
apomorphine, oxytocin or NMDA in male rats. Of
particular importance is the finding that this
inhibitory effect of muscimol occurs together
with a concomitant reduction of the NO,and N03-
increase usually found in the paraventricular
dialysale when these behavioural responses are
induced by the above compounds. As baclofen,
which is several times more active than muscimol
on GABAb receptors, is unable to prevent these
responses, and the musciniol effect is abolished
by bicuculline, a GABAa receptor antagonist,
muscimol apparently reduces penile erection,
yawning and the paraventricular N02- and N03-
increase induced by the above compounds by
stimulating GABAa receptors in the PVN. As
penile erection and yawning are apparently
mediated by the activation of NO synthase
present in paraventricular oxytocinergic neurons
projecting to extrahypothalainic brain
areas, which mediate these behavioural
responses, it is likely that these GABAa
receptors are located on the cell bodies of
these oxytocinergic neurons (see above). As
GABAergic synapses impinge on parvocellular and
magnocellular oxytocinergic neurons, the finding
suggests that GABAergic synapses also impinge on
and control (in an inhibitory fashion)
oxytocinergic neurons mediating penile crection
and yawning by interfering with the mechanisms
activated by apomorphine, oxytocin and NMDA,
which lead to the activation of NO synthase. As
expected, muscimol reduces not only penile
erection and yawning but also the
paraventricular NO2- and N03 increase induced by
NMDA at doses lower than those required to
reduce these responses induced by oxytocin and
apomorphine.
This higher sensitivity of NMDA-induced
activation of oxytocinergic neurons mediating
penile erection and yawning to GABAergic
inhibition when compared to that induced by
apomorphine and oxytocin, may be due to the fact
that muscimol acts not only on GABAa receptors
located in the cell bodies of oxytocinergic
neurons to inhibit their activation by NMDA,
apomorphine or oxytocin, but also on GABAergic
receptors that control an endogenous excitatory,
(possibly glutamatergic) input to oxytocinergic
neurons. This would cause, in turn, a decrease
in the release of endogenous glutamic acid,
thereby producing a more pronounced inhibition
of oxytocinergic neurons, which renders them
less sensitive to injected exogenous NMDA.
In line with this hypothesis, excitatory
glutamatergic synapses impinge on
paraventricular oxytocinergic neurons.
Altematively, the higher doses of muscimol
required to reduce apomorphine and oxytocin
responses, when compared to NMDA responses, may
simply reflect the different molecular
mechanisms mediating apomorphine- oxytocin- and
NMDA-induced penile erection and yawning.
Namely, although a Ca2+ influx apparently
mediates NMDA-, apomorphine and oxytocin-induced
penile erection, yawning and the paraventricular
NO2- and N03- increase, NMDA induces these
responses by acting on NMDA receptorcoupled,
voltage-dependent Ca 2+ channels, while
apomorphine and oxytocin activate
conotoxin-GVIA-sensitive Ca2+ channels. Whatever
mechanism may be responsible for the different
sensitivity to muscimol of NMDA, oxytocin and
apomorphine responses, muscimol prevents penile
erection, yawning and paraventricular NO2- and
NO3- increase induced by all the above
compounds, suggesting that GABA exerts an
inhibitory control on oxytocinergic neurons
mediating these responses, as found with other
oxytocinergic neurons. Accordingly, GABA
inhibits oxytocin release induced by suckling
and by osmotic stimuli.[...]
