Endogenous opioids tonically inhibit the depressor neurones in the caudal ventrolateral medulla of rabbits: Mediation through δ- and ϰ-receptors

In the present studies, an attempt was made to elucidate the role of endogenous opioid inputs to the depressor region of the caudal ventrolateral medulla in the tonic regulation of arterial pressure and to examine the subtype(s) of receptor underlying any observed effects by use of receptor-specific antagonists. The depressor region of the caudal ventrolateral medulla in chloralose-anesthetized, artificially ventilated rabbits was functionally identified by injection of l-glutamate (5 nmol). Bilateral injection of the non-selective opioid antagonist naloxone (0.3, 5 and 20 nmol) into the caudal ventrolateral medulla produced a dose-dependent depressor response, accompanied by a bradycardia, suggesting a tonically active inhibitory opioid input to this region. Bilateral injection of the selective δ-receptor antagonist ICI 174,864 (0.3 nmol) or of the κ{script}-receptor antagonist nor-binaltorphimine (1 nmol), also markedly reduced both arterial pressure and heart rate. In contrast, injection of the μ-selective antagonist β-funaltrexamine (0.3-0.6 nmol) produced no effect on arterial pressure or heart rate. These data support the hypothesis that tonically active endogenous opioid inputs, possibly enkephalinergic and/or dynorphinergic, inhibit the depressor neurones of the caudal ventrolateral medulla in the rabbit through activation of δ- and κ{script}-receptors. Surprisingly, injection of the opioid agonists leu-enkephalin (1 nmol) or dynorphin 1-13 (0.1 nmol), but not the selective μ-receptor agonist DAGO (1 nmol), in the depressor area of the caudal ventrolateral medulla also induced naloxone-sensitive (5 mg/kg, i.v.) decreases in both arterial pressure and heart rate. While this finding may merely reflect the difficulties associated with the use of exogenous agonists, as compared to antagonists, in the study of endogenous transmitter systems, the depressor effects observed with the agonists could also reflect the presence of different populations of opioid receptors in the caudal ventrolateral medulla.