Central cardiovascular actions of d-Ala²-Met⁵-enkephalinamide in the rat: Effects of naloxone and nucleus reticularis gigantocellularis lesion

In pentobarbital-anesthetized rats, intraventricular administration of d-Ala²-Met⁵-enkephalinamide (d-Ala, 30, 100 or 300 nmol/kg) dose-dependently elicited a reduction in arterial pressure. This d-Ala-promoted hypotension was significantly antagonized by naloxone pretreatment (3 mg/kg, i.c.v.) and attenuated by bilateral focal nucleus reticularis gigantocellularis (NRGC) lesions. At higher doses, d-Ala also produced a delayed hypertension that was not only unaffected by naloxone or NRGC lesions, but was in fact potentiated by such pretreatments. We speculate that d-Ala may produce its cardiovascular effect by activating separate subclasses of opiate receptors, possibly at different neural substrates that include the NRGC.