Effect of withdrawal from chronic naltrexone on regional cerebral oxygen consumption in the cat

Abstract

This investigation determined the effects of withdrawal from chronic naltrexone administration on average and regional cerebral blood flow, oxygen extraction and oxygen consumption. The relationship between the effects of withdrawal from chronic administration of this opiate receptor antagonist, which may increase the numbers of postsynaptic opiate receptors, and these parameters was investigated. Fourteen adult mongrel cats were administered subcutaneous injections of 1 mg/kg naltrexone HCl or 1 ml 0.9% saline twice daily for 21 days. Two days later, regional cerebral blood flow was monitored using radioactively tagged microspheres. The animals were sacrificed and prepared for microspectrophotometric analysis of regional cerebral venous and arterial oxygen saturation. Regional cerebral oxygen consumption was calculated as the product of cerebral blood flow and oxygen extraction for each area examined. After 2 days of withdrawal from chronic naltrexone treatment, the blood pressure, heart rate and blood gas parameters did not change significantly when compared to saline-treated animals. Average cerebral blood flow was significantly increased from 47.9 ± 3.4ml/min/100 g (mean ± S.E.M.) in the control group to 80.3 ± 6.5 (ml/min/100 g) in the chronic naltrexone-treated group. Flow was significantly increased in the cortex, lenticulate nuclei, thalamus and pons. Neither average cerebral oxygen consumption, which increased slightly, nor cerebral oxygen extraction, which decreased slightly, were significantly altered by treatment. The distribution of flow among the examined regions was, however, significantly altered in the animals 2 days after receiving chronic naltrexone injections. These changes were not restricted to brain regions dense in neuronal opiate receptors. There was no relationship between the increased number of opiate receptors, which have been reported to occur during and immediately after treatment with naltrexone, and cerebral oxygen consumption. Withdrawal from chronic naltrexone administration may have a direct effect on the cerebral vasculature.