Cardiovascular and behavioural effects induced by naloxone-precipitated morphine withdrawal in rat: characterization with tachykinin antagonists

Abstract

This study examined the intracerebroventricular (i.c.v.) effects of three selective tachykinin receptor antagonists on the cardiovascular and behavioural responses induced by naloxone-precipitated morphine withdrawal in rats. I.c.v. injection of naloxone (10 μg) to morphine pre-treated rats (i.c.v. for 5 days) induced an immediate increase in blood pressure (∼10 mmHg) and behavioural activity (sniffing > rearing > face washing ∼ grooming ∼ wet dog shake) without causing significant heart rate changes. The prior i.c.v. injection of the NK 1 receptor antagonist (6.5 nmol LY306740) reduced face washing and grooming during morphine withdrawal. NK 2 and NK 3 receptor antagonists (6.5 nmol SR48968 and R820) did not affect behavioural effects, yet the co-injection of the three tachykinin antagonists reduced all behavioural activity. The pressor response was not affected by the selective inhibition of NK 1 and NK 3 receptors while both blood pressure and heart rate were markedly enhanced by SR48968 during morphine withdrawal. The potentiating effect of SR48968 was prevented following simultaneous blockade of the three tachykinin receptors. In addition to confirming the involvement of central tachykinins in behavioural manifestations to morphine withdrawal, data suggest a modulatory function for tachykinins, especially the NK 2 receptor, in brain autonomic control of blood pressure and heart rate in supraspinal noloxone-precipitated withdrawal.