Cannabinoid and GABA modulation of sympathetic nerve activity and blood pressure in the dorsal periaqueductal gray of the rat

Sympathoexcitation and increased blood pressure evoked by central networks integrating defensive behavior are fundamental to the acute stress response. A balance between excitatory glutamatergic and inhibitory GABAergic neurotransmission in the dorsal periaqueductal gray (dPAG) results in a tonic level of activity in the alerting system. Neuromodulators such as endocannabinoids have been shown to influence the sympathoexcitatory and pressor components of acute stress in the dPAG, exemplified by the defense response as a model, but the mechanism of integration remains unknown. The present study examines the role of GABA and its interaction with endocannabinoids in modulating sympathetic nerve activity and blood pressure related to the defense response. Microinjection of the broad-spectrum excitatory amino acid dl-homocysteic acid (DLH) identified sites of the defense pathway in the dPAG from which an increase in renal sympathetic nerve activity and blood pressure could be evoked, and subsequent microinjections were made at the same site through a multibarrelled micropipette. Blockade of GABAA receptors or microinjection of the cannabinoid 1 receptor agonist anandamide elicited a renal sympathoexcitation and pressor response. Prior microinjection of the GABAA receptor antagonist gabazine attenuated the sympathoexcitation and pressor response associated with anandamide microinjection. In contrast, the sympathetic response to DLH was enhanced by GABAA receptor blockade. These data demonstrate that sympathoexcitatory neurons in the dPAG are under tonic inhibition by GABA and that endocannabinoids modulate this GABAergic neurotransmission to help regulate components of the defense response.