BLOCKADE OF ALPHA-2-ADRENERGIC RECEPTORS IN THE ROSTRAL VENTROLATERALMEDULLA ATTENUATES THE SYMPATHOINHIBITORY RESPONSE TO COCAINE

The purpose of this study was to determine whether neurons in the rost ral ventrolateral medulla play a role in the sympathoinhibitory respon se elicited by i.v. administration of cocaine and, if so, to identify the type(s) of receptors involved. Adrenergic antagonists were microin jected bilaterally into the rostral ventrolateral medulla in pentobarb ital-anesthetized rats in an attempt to block the decrease in sympathe tic nerve discharge (SND) elicited by cocaine (1 mg/kg i.v.). After th e bilateral microinjection of saline, cocaine elicited a -56 +/- 5% (m ean +/- S.E.) decrease in SND lasting 36 +/- 3 min. Cocaine also incre ased arterial pressure (21 +/- 3 mm Hg). Prior microinjection of the a lpha-2 adrenergic antagonist idazoxan (0.3, 3 or 10 nmol) did not alte r the magnitude of the sympathoinhibitory response to cocaine; however , the duration of the response was significantly reduced by all 3 dose s (range 21 +/- 3 to 11 +/- 2 min). Similarly, microinjection of the a lpha-2 adrenergic antagonist piperoxan (10 nmol) decreased the duratio n (from 45 +/- 8 to 23 +/- 4 min), but not the magnitude of the sympat hoinhibitory response. Microinjection of either the alpha-1 adrenergic antagonist terazosin (0.24 nmol) or the beta adrenergic receptor anta gonist propranolol (2 nmol) did not attenuate the decrease in SND elic ited by cocaine. The cocaine-mediated presser response was not affecte d by any of the antagonist treatments. These data show that the decrea se in SND elicited by cocaine is mediated centrally and involves, at l east in part, the activation of alpha-2 adrenergic receptors in the ro stral ventrolateral medulla.