The activation of central cannabinoid receptors inhibits salivary secretion

FERNANDEZ SOLARI, JAVIER; PRESTIFILIPPO, J.P; VISSIO, PG; MC CANN, S.; RETTORI, V.; ELVERDIN, J.C.

Tihany, Hungria

Simposio; 16TH ANNUAL SYMPOSIUM ON THE CANNABINOIDS; 2006

International Cannabinoid Research Society

THE ACTIVATION OF CENTRAL CANNABINOID RECEPTORS INHIBITS SALIVARY SECRETION   It is known that Δ9 –tetrahydrocannabinol modulates autonomic neurotransmission. Therefore, we hypothesized that the central endocannabinoid system would also modulate salivary secretion by acting on the autonomic nervous system. Several studies suggest that the lateral preoptic-hypothalamic region is an important center for eliciting salivary secretion through pre-ganglionic parasympathic nerves that project to yhe salivary gland in the rat. Morover, in this syudy we found by immunohistochemical techniques that type 1 cannabinoid receptor (CB1-r) are densely distributed in the lateral hypothalamic area of adult male Wistar rat, supporting the hipótesis of autonomic modulation by the endocannabinoid system. In addition, we observed that the endocannabinoid anandamide (AEA, 50 ng/5µl vehicle) injected into the lateral cerebral ventricle (i.c.v) reduced significantly the salivary secretion induced by increasing doses of metacholine injected i.v. This inhibitory efect was partially but significantly blocked by previous i.c.v injection of the CB1-r antagonist, AM251 (500 ng/5µl vehicle), and totally blocked by previous injection of bicuculline (25 ng/5µl saline), a GABAA receptor antagonist. The i.c.v injection of saline or vehicle had no effect on salivary secretion. These results suggest that AEA inhibits saliva secretion by increasing GABAergic activity that inhibits the parasympathetic neurotransmission, since when the rats were decentralized by cutting the corda tympani nerve, AEA injection was without effect. Morover, the parasimpathetic decentralization per se  caused an inhibition of saliva secretion equivalent to the produced by AEA. On the contrary, when the superior cervical ganglion, a sympathetic ganglion, was removed, the inhibitory effect of AEA injection remained unaltered.