EFFECTS OF BETA-FNA ON SYMPATHOADRENAL, CARDIOVASCULAR, AND ANALGESICRESPONSES TO DAMPGO AT REST AND DURING STRESS

To elucidate further the role of mu-opioid receptors in mediating anal gesia and cardiovascular function at rest and during stress, rats were pretreated ICV with either saline (5 mu l) or beta-funaltrexamine (be ta-FNA, 5 nmol/5 mu l), a noncompetitive opioid receptor antagonist th at inactivates irreversibly mu receptors, 2 days prior to [D-Ala(2),N MePhe(4),Gly(5)-ol]enkephalin (DAMPGO, 1 nmol, ICV) administration. Pr etreatment with beta-FNA blocked DAMPGO-induced analgesia as measured by the tail-flick test. DAMPGO also produced an increase in blood pres sure (BP), sympathoadrenal outflow, and a bradycardia. Pretreatment wi th beta-FNA converted the DAMPGO-induced bradycardia to a tachycardia, significantly reduced the DAMPGO-induced increase in epinephrine by 6 0%, and the norepinephrine response by 45%, and attenuated mildly the increase in BP due to DAMPGO. In saline-treated rats, restraint stress evoked an increase in HR, BP, and plasma calecholamines. Pretreatment with beta-FNA partially attenuated the increase in HR in response to stress. In the presence of DAMPGO, restraint stress resulted in a furt her bradycardia, which was significantly blocked by pretreatment with beta-FNA. Stress also produced increases in BP and plasma catecholamin es, which were not prevented by pretreating rats with beta-FNA. These results indicate that beta-FNA may not have inactivated all the recept ors accessible to DAMPGO which control BP, or alternatively, beta-FNA may selectively inactivate a subtype of mu receptors. In addition, bra in mu opioid receptors appear to be significantly involved in mediatin g supraspinal analgesia and regulating parasympathetic outflow to the heart and sympathoadrenal release of catecholamines.