Effects of endocannabinoids on discharge of baroreceptive NTS neurons. Neurosci Lett 2005 Jun 24;381(3):334-9
Date
05/18/2005Pubmed ID
15896495DOI
10.1016/j.neulet.2005.02.044Scopus ID
2-s2.0-19344369593 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
Previously, we have shown that microinjection of endocannabinoids (ECBs) into the nucleus tractus solitarius (NTS) can modulate baroreflex control of blood pressure (BP), prolonging pressor-induced inhibition of renal sympathetic nerve activity. This suggests that ECBs can modulate excitability of baroreceptive neurons in the NTS. Studies by others have shown that neural cannabinoid (CB1) receptors are present on fibers in the NTS, suggesting that some presynaptic modulation of transmitter release could occur in this region which receives direct afferent projections from arterial baroreceptors and cardiac mechanoreceptors. This study, therefore, was performed to determine the effects of ECBs on NTS baroreceptive neuronal discharge. Picoinjection of the ECB anandamide (AEA) was found to significantly increase discharge of baroreceptive neurons (20 of 23). Picoinjection of the ECB uptake inhibitor, AM404, which enhances endogenous ECB activity, also significantly increased discharge of baroreceptive neurons (8 of 10 neurons). To determine if effects of ECBs involved a GABAA mechanism, the neuronal responses to AEA and AM404 were tested after prior blockade of postsynaptic GABAA receptors by bicuculline (BIC) or SR 95531 hydrobromide (gabazine--SR 95531), which would eliminate any effects due to modulation of GABA input. The increase in neuronal discharge to both AEA and AM404 was significantly attenuated following BIC or SR 95531, which alone significantly increased discharge of baroreceptive neurons tested. These results support the hypothesis that ECBs enhance baroreflex function through increases in NTS baroreceptive neuronal activity, due in part to modulation of GABAergic inhibitory effects at the neuronal level.
Author List
Seagard JL, Hopp FA, Hillard CJ, Dean CAuthor
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsArachidonic Acids
Cannabinoid Receptor Modulators
Endocannabinoids
GABA Antagonists
Injections, Intraventricular
Male
Neurons
Pressoreceptors
Rats
Rats, Sprague-Dawley
Receptors, GABA-A
Solitary Nucleus