Changes in sympathetic nerve activity during morphine abstinence in the rat.

Abstract

The aim of the study was to examine sympathetic nerve activity, heart rate and blood pressure during naloxone-precipitated withdrawal reactions in morphine-dependent rats. In two groups of rats, one group conscious and the other anaesthetized with chloralose, renal sympathetic nerve activity (rSNA), heart rate (HR) and mean arterial blood pressure (MAP) were recorded before and during naloxone-precipitated abstinence. The conscious rats showed a biphasic pattern in the withdrawal responses. Initially, after small doses of naloxone, rSNA and HR increased and increased somatomotor activity including 'wet-dog' shakes were observed. However, upon further administration of naloxone, rSNA and HR promptly decreased while MAP increased. As rSNA was lowered, the withdrawal behaviour of the rats was markedly diminished and the animals rested calmly in the cages. In contrast, the anaesthetized group reacted with an immediate decrease in rSNA after the lowest dose of naloxone, followed by an increase in MAP and HR after higher doses of naloxone, although rSNA was still decreased. In both groups, rSNA remained below pre-naloxone control levels when the increased MAP was lowered to the pre-naloxone level with sodium nitroprusside, indicating a central origin of the sympathetic inhibition. It is concluded that naloxone elicits a biphasic rSNA response in the conscious, morphine-dependent rat. This includes an initial increase upon low naloxone doses followed by a pronounced inhibition of rSNA after higher doses. In chloralose-anaesthetized rats, rSNA declined already after low doses of naloxone. It is suggested that there might be a tonic, excitatory input on rSNA, mediated by the activation of opiate receptors by high levels of circulating morphine in the addicted animal. Naloxone will therefore decrease the tonic sympathetic nerve activity in these rats.