Effects of heroin and naloxone on cerebral blood flow in the conscious rat

Abstract

The widespread, heterogeneous distribution of opiate receptors and their endogenous ligands in the nervous system are reflective of the variety of central and systemic effects seen after opiate administration. Most neurons respond to either systemic or local opiate application with a decrease in firing rate, although increased neuronal activity has also been reported in such regions as the caudate, amygdala, ventral tegmentum, and substantia nigra. While regional metabolic studies have consistently reported neuronal suppression, some portion of this might be secondary to systemic hypercapnia. Using a brief blood flow marker, we recently reported a heterogenous increase in activity in more than half of the brain regions examined. To extend that study, we report herein the results of a dose-response and antagonist challenge experiment. Rats received an acute injection of one of the following: heroin (0.1, 0.3 or 1.0 mg/kg), naloxone (1.0 mg/kg), a cocktail of heroin (0.3 mg/kg) plus naloxone or saline. One min after drug administration, 160 μCi/kg [1-¹⁴C] octanoate, a marker for cerebral blood flow, was delivered IV. Rats were sacrificed two min later, brains removed and prepared for autoradiography. Of the fifty-eight areas analyzed, heroin caused an increase in blood flow in the caudate, claustrocortex, laterodorsal thalamus and dentate gyrus. Decreases were found for the bed nucleus of the stria terminalis, preoptic area, basolateral nucleus of the amygdala, dorsomedial and paraventricular hypothalamus, entorhinal and cingulate cortices and dorsal raphe. Naloxone resulted in significant increases in the olfactory tubercle and paraventricular nucleus while decreases were seen in the cingulate and basolateral amygdala.