patients
induced by naltrexone
challenge during detoxification.
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.
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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.
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