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KMID : 0361520010120010032
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Korean Journal of Psychopharmacology
2001 Volume.12 No. 1 p.32 ~ p.41
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Effects of Naltrexone on the Tyrosine Hydroxylase Expression in the Hypothalamic Areas in Rats with Chronic Ingestion of 5% Ethanol
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이기철/Gi Chul Lee
오세중/이정호/정홍경/하준명/정재현/이대환/김도형/정주호/Se Joong Oh/Jung Ho Lee/Hong Kyung Jung/Jun Myung Ha/Jae Hyun Jeong/Dae Hwan Lee/Doh Hyung Kim/Joo Ho Chung
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Abstract
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This study was designed to evaluate the effects of nonselective opioid
antagonist naltrexone on the expression of tyrosine hydroxylase （TH） in variable
areas of hypothalamus in rats with chronic ingestion of 5% ethanol using
immunohistochemical measures. Methods：To induce polydipsia with 5% ethanol,
Spraque-Dawley rats were placed in automatic cage where a pellet dispenser
automatically dispensed 90 mg pellets at fixed time 60 seconds （FT 60s） feeding
schedule over 150-minute test session. After 4 weeks of daily exposure to the FT 60s
feeding schedule, experimental rats were administered naltrexone （0.25 mg/kg, i.p）,
vehicle （1 cc/kg, i.p） for 3 weeks. After completing the 3 weeks of naltrexone and
vehicle injections, the polydipsic rats were sacrificed. The brains were removed and
postfixed in the same overnight fixation, then frozen sections of 40 μM thickness
were made in the coronal plane. Sections were stained for detection of tyrosine
hydroxylase （TH） according to the immunohistochemical method. Results：1） Both
experimental animals with schedule-induced polydipsia （SIP） and the bolus with 5%
ethanol control showed significant increase in the amounts of 5% ethanol ingestion as
compared with their baseline. The naltrexone treated group showed significant decrease
in the amount of 5% ethanol ingestion at 2nd and 3rd week as compared with their
baseline. Meanwhile, the vehicle control showed no changes in the amount of 5% ethanol
ingestion for 3 weeks as compared with their baseline. 2） There was diffused and
definite decreases in the TH immunoreactive cells in the bolus control with chronic
ingestion of 5% ethanol. The SIP with water group showed marked increase in TH
immunoreactive cells in the paraventricular nucleus and the periventricular
hypothalamic nucleus. The SIP with 5% ethanol group showed definite decrease of TH
immunoreactive cells in the paraventricular nucleus and the periventricular
hypothalamic nucleus. The naltrexone treated group showed significant increase of TH
immunoreactive cells in the paraventricular nucleus but no changes in the
periventricular hypothalamic nucleus. Conclusion：These results suggest that the fixed
time feeding procedure for schedule induced polydipsia as an animal model of
alcoholism was not suitable. The author identified that naltrexone has suppressed the
ingestion of ethanol. The chronic ingestion of 5% ethanol suppress the TH
immunoreactive cells in the paraventricular nucleus and the periventricular
hypothalamic nucleus. Naltrexone increases the TH immunoreactive cells which was
suppressed by chronic ingestion of 5% ethanol in the paraventricular nucleus.
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