Delta9-tetrahydrocannabinol inhibits gastric motility in the rat through cannabinoid CB1 receptors.
We investigated involvement of the autonomic nervous system in gastric motor and cardiovascular responses to delta9-tetrahydrocannabinol (delta9-THC) in anesthetized rats. Intravenously administered delta9-THC evoked long-lasting decreases in intragastric pressure and pyloric contractility, bradycardia, and hypotension. The changes in gastric motor function and bradycardia were abolished by vagotomy and ganglionic blockade, whereas spinal cord transection prevented the hypotensive response. Administered intravenously alone, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-met hyl-1H-pyrazole-3-carboxamide, a putative cannabinoid CB1 receptor antagonist, evoked transient decrease in intragastric pressure, and hypertension that was associated with bradycardia. However, this agent completely blocked the gastric motor and cardiovascular responses to intravenous delta9-THC. Application of delta9-THC to the dorsal surface of the medulla resulted in small and short-lasting decreases in gastric motor and cardiovascular function. We conclude that the decrease in gastric motor function and bradycardia are partially due to an action of delta9-THC in the dorsal medulla and that intact vagal nerves are required. The hypotension was mediated through sympathetic pathways. Both gastric motor and cardiovascular effects of peripherally administered delta9-THC seem to be mediated through cannabinoid CB1 receptors.
Krowicki
Z K
ZK
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans 70112, USA. zkrowi@lsumc.edu
Moerschbaecher
J M
JM
Winsauer
P J
PJ
Digavalli
S V
SV
Hornby
P J
PJ
D000818:Animals; D001933:Brain Stem / Q000187:drug effects*; D013759:Dronabinol / Q000494:pharmacology*; D005730:Ganglionic Blockers / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries; D014628:Vagotomy
D005730:Ganglionic Blockers; D013759:Dronabinol