Delta(9)-tetrahydrocannabinol inhibits gastric motility in the rat throughcannabinoid CB1 receptors

We investigated involvement of the autonomic nervous system in gastric moto r and cardiovascular responses to ag-tetrahydrocannabinol (Delta(9)-THC) in anesthetized rats. Intravenously administered Delta(9)-THC evoked long-las ting decreases in intragastric pressure and pyloric contractility, bradycar dia, and hypotension. The changes in gastric motor function and bradycardia were abolished by vagotomy and ganglionic blockade, whereas spinal cord tr ansection prevented the hypotensive response. Administered intravenously al one, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamide, a putative cannabinoid CB1 receptor antagonist, evoked transient decrease in intragastric pressure, and hypertension that w as associated with bradycardia. However, this agent completely blocked the gastric motor and cardiovascular responses to intravenous Delta(9)-THC. App lication of Delta(9)-THC to the dorsal surface of the medulla resulted in s mall and short-lasting decreases in gastric motor and cardiovascular functi on. We conclude that the decrease in gastric motor function and bradycardia are partially due to an action of Delta(9)-THC in the dorsal medulla and t hat intact vagal nerves are required. The hypotension was mediated through sympathetic pathways. Both gastric motor and cardiovascular effects of peri pherally administered Delta(9)-THC seem to be mediated through cannabinoid CB1 receptors. (C) 1999 Elsevier Science B.V. All rights reserved.