Related Experiment Video
Updated: Aug 12, 2026
A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training
Published on: January 29, 2017
Regional cerebral blood flow changes in chronic alcoholic patients induced by naltrexone challenge during
A M Catafau1, A Etcheberrigaray, J Perez de los Cobos
1Nuclear Medicine Department, Hospital de Sant Pau, Barcelona, Spain.
Unlabelled:
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.
Insights
Naltrexone, used for alcohol dependence, reduces regional cerebral blood flow (rCBF) in the basal ganglia and mesial temporal regions of alcoholics. This neurophysiological effect supports the opioid system
Area of Science:
- Neuroscience
- Addiction Medicine
- Radiology
Background:
- Naltrexone is an opioid antagonist used for alcohol dependence, primarily based on animal models.
- The neurophysiological mechanisms of naltrexone's effects in alcoholic patients are not well understood.
- Endogenous opioid system involvement in alcohol drinking and dependence is suggested by behavioral studies.
Purpose of the Study:
- To investigate the effects of naltrexone on regional cerebral blood flow (rCBF) in chronic alcoholic patients during detoxification.
- To explore the neurophysiological underpinnings of naltrexone's therapeutic action in alcohol dependence.
Main Methods:
- Sixteen alcoholic inpatients underwent two brain SPECT scans using 99mTc-hexamethyl propyleneamine oxime (HMPAO).
- Scans were performed during abstinence (baseline) and after oral administration of 150 mg naltrexone.
- Region-to-cerebellar ratios were calculated for various brain regions, and percentage change in rCBF was determined; data were compared to controls.
Main Results:
- Alcoholic patients exhibited lower baseline rCBF in the orbitofrontal and prefrontal cortex compared to controls.
- Following naltrexone administration, a significant decrease in rCBF was observed in the left and right basal ganglia and the left mesial temporal region.
- These decreases in rCBF were statistically significant when compared to test-retest values in normal volunteers.
Conclusions:
- The observed rCBF decrease in opioid receptor-rich areas (basal ganglia, mesial temporal region) suggests reduced metabolic activity following naltrexone challenge.
- These findings support the involvement of the opioid system in alcohol dependence.
- The localization of naltrexone-induced rCBF changes highlights the potential role of emotional memory and obsessive-compulsive pathways in craving and treatment efficacy.
