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Received April 29, 2004
Revised May 24, 2004
Accepted after revision July 20, 2004
1 Tulane University
* To whom correspondence should be addressed. E-mail: bnsmith{at}tulane.edu.
Cannabinoids bind central type 1 receptors (CB1R) and modify autonomic functions, including feeding and antiemetic behaviours, when administered peripherally or into the dorsal vagal complex. Western blots and immunohistochemistry indicated CB1R expression in the rat dorsal vagal complex, and tissue PCR confirmed that CB1R message was made within the region. To identify a cellular substrate for the central autonomic effects of cannabinoids, whole-cell patch-clamp recordings were made in brainstem slices to determine the effects of CB1R activation on synaptic transmission to neurones of the dorsal motor nucleus of the vagus (DMV). A subset of these neurones was identified as gastric-related after being labelled retrogradely from the stomach. The CB1R agonists, WIN55,212-2 or anandamide decreased the frequency of spontaneous excitatory or inhibitory postsynaptic currents in a concentration-related fashion, an effect that persisted in the presence of tetrodotoxin. Paired-pulse ratios of electrically-evoked postsynaptic currents were also increased by WIN55,212-2. The effects of WIN55,212-2 were sensitive to the selective CB1R antagonist, AM251. Cannabinoid agonist effects on synaptic input originating from neurones in the nucleus tractus solitarius (NTS) were determined by evoking activity in the NTS with local glutamate application. Excitatory and inhibitory synaptic inputs arising from the NTS were attenuated by WIN-55,212-2. Our results indicate that cannabinoids inhibit transfer of synaptic information to the DMV, including that arising from the NTS, in part by acting at receptors located on presynaptic terminals contacting DMV neurones. Inhibition of synaptic input to DMV neurones likely contributes to the suppression of visceral motor responses by cannabinoids.
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