Synergistic centrally mediated cardiovascular effects of a kappa opioid agonist and an alpha2-adrenoceptor agonist

In this study, we determined possible additive and synergistic centrally mediated hypotensive and bradycardic effects of U-62,066E, a nonpeptide kappa opioid agonist acting on the hippocampal formation (HF), and guanabenz, an alpha2-adrenoceptor agonist acting on the rostral ventrolateral medulla (RVLM), the nucleus tractus solitarius (NTS), or the locus coeruleus (LC). The drugs were microinjected at various doses into these areas of alpha-chloralose-anesthetized Sprague-Dawley rats. There were synergistic hypotensive and bradycardic effects between low, noneffective doses of U-62,066E acting on the HF and guanabenz acting simultaneously on the RVLM. Higher doses of each agent, which themselves caused hypotension and bradycardia acting on each brain area alone, did not lead to synergistic effects when the drugs were injected simultaneously into those areas. There were no synergistic effects between U-62,066E acting on the HF and guanabenz acting on the NTS or the LC.