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mise à jour du
9 décembre 2004
Brain Research
1990; 537; 163-168
Septohippocampal cholinergic pathway and penile erections induced by dopaminergic and cholinergic stimulants
Noriaki Maeda, Nobuya Matsuoka and Isamu Yamaguchi
Basic Research Group, Tsukuba Research Laboratories, Ibaraki (Japan)

Chat-logomini

It has been reported that the direct and indirect dopaminergic stimulants, apomorphine and amantadine, induce- penile erections in male rats. Penile erection was attenuated by both dopaminergic and cholinergic antagonists, suggesting that dopaminergic stimulation causes cholinergic activation.
 
There have been papers on studies of the sites of the interaction. An involvement of the septum and striatum has been indicated from a study on apomorphine-induced yawnings which occur simultaneously with penile erections. In contrast, Melis et al. proposed that the paraventricular nucleus of the hypothalamus (PVN) is the area of the brain where dopamine agonists act to induce penile erection and yawning.
 
Electrophysiological studies, however, suggest that the hippocampus has a crucial role in expressing penile erections. This brain area is sparsely innervated by dopaminergic nerves, while densely innervated by cholinergic nerve fibers derived from cells in the medial septum. Furthermore, the cells in the septum receive inhibitory influences from the A10 dopaminergic cell bodies.
 
In the present paper, we studied the effects of septohippocampal denervation on penile erections induced by dopaminergic and cholinergic stimulants. The denervations were achieved either by medial septum or fimbria-fornix lesions. [...]
 
DISCUSSION
 
It is a novel finding that penile erections are elicited in rats by systemic administration of pilocarpine. The pilocarpine-induced penile erections were attenuated by scopolamine but not by methylscopolamine. These results suggest that an activation of central muscarinic receptors is responsible for the penile erection. However, Gower et al. reported that physostigmine did not elicit penile erections. Differences in the specificity of the action of pilocarpine and physostigmine might explain this discrepancy. Physostigmine inhibits cholinesterases, no doubt stimulating nicotinic receptors as well as muscarinic receptors. Furthermore, muscarinic receptors are now divided into Ml, M2 and M3 subtypes. Pilocarpine is reported to be more specific for muscarinic Ml receptors'. At low doses of pilocarpine, penile erection may be induced by preferential stimulation of Ml subtype, whereas at higher doses, the score of penile erection tended to decline, presumably due to its general stimulation of these subtypes. There seems to be a marked difference in the frequency of basal penile erections in the two studies. Control rats in the present study showed considerable number of penile erections (0.3-0.7 times/h), while those observed by Gower et al. showed minimal erections. Central cholinergic tone may be depressed in the latter experiment. Our rats were subjected to handling prior to use, which could be responsible for the difference.
 
McLean, after a series of electrophysiological studies, concluded that the hippocampus and its afferents are important for the expression of penile erections. The hippocampus is densely innervated by, cholinergic nerve fibers which originate from the septum and course through the fimbria-fornix. In the present study, medial septum and fimbria-fornix lesions decreased hippocampal ChAT activity by 45.2 and 93.7%, respectively, and abolished amantadine- and apomorphine- but not pilocarpine-induced penile erections. Furthermore, scopolamine but not methylscopolamine suppressed the penile erections induced by amantadine and apomorphine in agreement with previous papers. It is thus speculated that intact cholinergic nerve activities are necessary for amantadine and apomorphine to induce penile erections. In contrast with these dopaminergic stimulants, pilocarpine may directly stimulate muscarnic receptors.
 
Sulpiride, a dopamine antagonist, attenuated penile erections induced by amantadine and apomorphine, but hardly affected those by pilocarpine. At first sight, these results, when combined with those mentioned above, would seem to suggest that the cholinergic and dopaminergic influences on penile erection might be mediated, respectively, through the septohippocampal cholinergic pathway and the dopaminergic innervation of the cholinergic cells of origin of that path. However, the septohippocampal cholinergic nerves receive an inhibitory influence from the dopaminergic cells of the A10 region , and dopaminergic antagonists such as halperidol or lesioning with 6-hydroxydopamine have been shown to increase acetylcholine turnover rate in the hippocampus. There is a belief that apomorphine activates postsynaptic dopamine receptors at higher doses, hence, if the dopaminergic drugs used here were acting at postsynaptic receptors in the septum, agonists should be expected to decrease penile erection and antagonists to increase it. The opposite was found to be the case. One might argue in the case of apomorphine that the low doses found effective in stimulating penile erection were acting preferentially at presynaptic autoreceptors in the septal region to reduce inhibition of the cholinergic neurons. However, this would not explain the very similar findings with amantadine which has been reported to indirectly stimulate the dopaminergic nerves and has not shown to have any such presynaptic action. The autoreceptor hypothesis has recently been questioned by many authors.
 
The alternative, therefore, is to consider that the primary action of the dopaminergic drugs with regard to penile erection is in some other brain region, with the effects being expressed through other, non-dopaminergic influences on the septohippocampal tract. In this respect, it is interesting to note the hypothesis proposed by Argiolas et al. that apomorphine interacts with postsynaptic dopamine receptors in the PVN of the hypothalamus to stimulate the activity of oxytocinergic neurons, which in turn mediate the appearance of penile erection. a Melanocyte stimulating hormone and adrenocorticotropic hormone both induce penile erections, and their activities are well correlated with the increase of acetylcholine turnover in the hippocampus. Such an activity might be shared with oxytocin.
 
Recently, several subtypes of dopamine receptors have been postulate. As apomorphine is known to act as a mixed D1-D2 agonist, it is probable that we see the combined effects mediated by these subtypes when apomorphine is administered systemically. Bitran et al. have shown that microinjection of quinelorane, a D2 agonist, into the medial preoptic area inhibited penile erection while apomorphine facilitated it. Activation of various subtypes of postsynaptic receptors in the incertohypothalamic dopaminergic system might occur at different concentrations of agonist and contribute to the bell-shaped dose-response curves. These possibilities remain to be elucidated.