Cannabinoid Receptor Modulation of the Defense Response in the Dorsal Periqueductal Gray

Abstract

The defense response is the coordinated reaction to physical and psychological stress, and has been validated as an experimental model of panic or fear. The hypothalamus and the midbrain periaqueductal gray (PAG) are key sites on the defense pathway from which sympathoexcitation, hypertension, tachycardia, increased muscle blood flow, analgesia, twitching of the vibrissae and hyperlocomotion can be evoked. Cannabinoids have been shown to be involved in anxiety‐related responses in the PAG and the present studies examined a role for cannabinoids in the mediation of the autonomic components of the defense response in the PAG. In anesthetized rats, microinjection of d,l‐homocysteic acid into the dorsal PAG could elicit a brisk sympathoexcitation, a pressor response and twitching of the whiskers. The hypothalamic defense area (HDA) was stimulated electrically at a site from which an intense sympathoexcitation and hypertension was evoked. The cannabinoid receptor (CB1R) antagonist AM251 was microinjected at the dorsal PAG site and the HDA stimulation was repeated. The renal sympathoexcitation was attenuated at 1 and 3 mins and the pressor response to HDA stimulation was attenuated at 3,5 and 10 mins post AM251. These data suggest that CB1R activation plays a role in the autonomic and cardiovascular responses of the defense response at the level of the dPAG. Supported by AHA Greater Midwest 0750010Z and NSF IOS 0751613.