Acute or chronic effects of cannabinoids on spontaneous or pharmacologically induced yawning in rats

Yawning is a reflex or event that is not fully understood. It is controlled by many neurotransmitters and neuropeptides and can be induced pharmacologically by cholinergic or dopaminergic agonists. Amongst their many actions, cannabinoids acting on cannabinoid (CB(1) or CB(2)) receptors can alter cholinergic and/or dopaminergic activity. This study examined the effects of Delta(8)-tetrahydrocannabinol (Delta(8)-THC) administered acutely (2.5 mg/kg intraperitoneally [ip], 15 min before test) or chronically (5 mg/kg for 30 days followed by 24 h or 7 days of discontinuation) on yawning induced by pilocarpine, a cholinergic agonist (0, 1, 2, 4 or 8 mg/kg ip), or apomorphine, a dopaminergic agonist (0, 20, 40 or 80 microg/kg subcutaneously [sc]). Acute effects of different doses of Delta(9)-tetrahydrocannabinol (Delta(9)-THC: 0, 0.5, 1.25 or 2.5 mg/kg ip) on yawning induced by pilocarpine (2 mg/kg ip) or apomorphine (40 microg/kg sc) were also investigated. Both pilocarpine and apomorphine produced yawning in a dose-related manner. Acute administration of Delta(8)-THC and Delta(9)-THC significantly reduced yawning induced by both pilocarpine and apomorphine. Chronic administration of Delta(8)-THC did not change yawning induced by either agonist 24 h or 7 days after discontinuation of Delta(8)-THC. However, a high frequency of spontaneous yawning was observed 7 days after Delta(8)-THC discontinuation. These results suggest that cannabinoid agonists inhibited yawning induced by cholinergic or dopaminergic agonists. In addition, the increased frequency of spontaneous yawning following cessation of chronic administration of a cannabinoid agonist may be of importance as a withdrawal sign for these drugs.