Zk. Krowicki et al., Delta(9)-tetrahydrocannabinol inhibits gastric motility in the rat throughcannabinoid CB1 receptors, EUR J PHARM, 371(2-3), 1999, pp. 187-196
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.