The recent introduction of the opioid antagonist naltrexone for alcohol-dependence therapy has been mainly based on behavioral animal models that provide evidence of the involvement of the endogenous opioid system in alcohol drinking and dependence. However, the neurophysiological mechanisms of the effect of naltrexone in alcoholic patients remain unknown. This study investigates the effects of a naltrexone challenge on regional cerebral blood flow (rCBF) in chronic alcoholic patients during detoxification.
Methods: Sixteen alcoholic inpatients underwent two 99mTc-hexamethyl propyleneamine oxime (HMPAO) brain SPECTs: a basal SPECT on day 10 of abstinence and a second SPECT on day 12 of abstinence after oral administration of 150 mg naltrexone. Region-to-cerebellar ratios were obtained for the orbitary frontal, prefrontal, lateral temporal and mesial temporal regions, basal ganglia and thalamus in each hemisphere. A percentage of rCBF change between both SPECTs was calculated for each region as 100 x (naltrexone - baseline)/ baseline. Values from 13 brain SPECTs of age-matched normal volunteers including test-retest measurements were used for statistical comparison.
Results: In baseline conditions, alcoholics showed lower rCBF than controls in left orbitofrontal cortex (84.0+/-5.1 versus 89.8+/-5.0, P < 0.01) and prefrontal cortex (left hemisphere: 87.4+/-5.2 versus 96.2+/-3.6, P < 0.001; right hemisphere: 87.0+/-4.9 versus 95.8+/-4.2, P< 0.001). After naltrexone, a significant rCBF decrease was found versus test-retest values in left basal ganglia (-3.3%+/-4.0% versus 1.5%+/-4.1%, P< 0.05), right basal ganglia (-4.2%+/-4.9% versus 0.6%+/-2.7%, P < 0.01) and left mesial temporal region (-4.5%+/-6.8% versus 2.2%+/-2.9%, P < 0.01).
Conclusion: The rCBF decrease detected by SPECT after naltrexone challenge in structures rich in opioid receptors, such as the basal ganglia and the left mesial temporal region, may reflect a naltrexone-induced decreased metabolic activity in these areas. These results support the involvement of the opioid system in alcohol dependence. Furthermore, the localization of naltrexone-induced rCBF changes in mesial temporal structures and in basal ganglia supports the implication of emotional memory and obsessive-compulsive phenomena in craving.