ETHANOL COUNTERACTION OF CLONIDINE-EVOKED INHIBITION OF NOREPINEPHRINE RELEASE IN ROSTRAL VENTROLATERAL MEDULLA OF RATS

Previous studies from our laboratory demonstrated an antagonistic hemo dynamic interaction between ethanol and clonidine in conscious and in urethane-anesthetized rats. The present study tested the hypothesis th at ethanol produces its effect by counteracting clonidine-evoked inhib ition of norepinephrine (NE) release at its major site of action, the rostral ventrolateral medulla (RVLM). In vivo electrochemical measurem ent of real-time changes in NE level in the RVLM of urethane-anestheti zed Sprague-Dawley rats was made along with blood pressure and heart r ate, Clonidine (30 mu g/kg, iv) produced significant decreases (p < 0. 05) in NE electrochemical signal and blood pressure. Ethanol (1 g/kg, iv) administered 10 min after clonidine significantly (p < 0.05) incre ased NE signal and counteracted clonidine-evoked hypotension. Equal vo lume of saline had no effect an NE signal in the RVLM nor on the hypot ensive response to clonidine. Pretreatment with the same dose of ethan ol (1 g/kg) caused slight increases in RVLM NE level and in blood pres sure, but did not influence the electrochemical and blood pressure res ponses to clonidine; clonidine (30 mu g/kg) administration 10 min afte r ethanol resulted in significant (p < 0.05) decreases in NE signal an d blood pressure. These findings suggest that: (i) ethanol counteracti on of the hypotensive action of clonidine involves, at least in part, opposite effects on central pathways that use NE as a neurotransmitter ; (ii) the RVLM represents a possible site for the adverse hemodynamic interaction between ethanol and clonidine; and (iii) ethanol-evoked i ncrease in RVLM NE, which correlates with its presser effect, is much enhanced when RVLM NE level is reduced by clonidine.