Effects of beta-FNA on sympathoadrenal, cardiovascular, and analgesic responses to DAMPGO at rest and during stress

To elucidate further the role of mu-opioid receptors in mediating analgesia and cardiovascular function at rest and during stress, rats were pretreated ICV with either saline (5 microliters) or beta-funaltrexamine (beta-FNA, 5 nmol/5 microliters), a noncompetitive opioid receptor antagonist that inactivates irreversibly mu receptors, 2 days prior to [D-Ala2, N MePhe4, Gly5-ol]enkephalin (DAMPGO, 1 nmol, ICV) administration. Pretreatment with beta-FNA blocked DAMPGO-induced analgesia as measured by the tail-flick test. DAMPGO also produced an increase in blood pressure (BP), sympathoadrenal outflow, and a bradycardia. Pretreatment with beta-FNA converted the DAMPGO-induced bradycardia to a tachycardia, significantly reduced the DAMPGO-induced increase in epinephrine by 60%, 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 catecholamines. Pretreatment with beta-FNA partially attenuated the increase in HR in response to stress. In the presence of DAMPGO, restraint stress resulted in a further bradycardia, which was significantly blocked by pretreatment with beta-FNA. Stress also produced increases in BP and plasma catecholamines, which were not prevented by pretreating rats with beta-FNA. These results indicate that beta-FNA may not have inactivated all the receptors accessible to DAMPGO which control BP, or alternatively, beta-FNA may selectively inactivate a subtype of mu receptors. In addition, brain mu opioid receptors appear to be significantly involved in mediating supraspinal analgesia and regulating parasympathetic outflow to the heart and sympathoadrenal release of catecholamines.