| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
In our experiments, the typical and atypical antidepressants were administered acutely or chronically into rats and hot plate analgesia, methionine-enkephalin-immunoreactivity (ME-I), <mu>-opioid receptor and <delta>-opioid receptor in various brain areas were investigated.
1. Acute effects of antidepressants
The single injection of imipramine (IMI) made no significant changes of ME-I in the frontal cortex, the limbic brain area, the striatum and the hypothalamus, except the hippocampus.
2. Chronic adminsistration of antidepressants.
Food pellets containig IMI, clomipramine (CLO) or mianserin (MIA) were edministered for 40 days to the rat.
(1) Analgesic effects of antidepressants were determined by the hot plate method. After 11 days treatment, the pain threshold significantly incereased, however, on the 39th day of treatment, no tolerance to nociceptive was detected.
(2) Methionine-enkephalin immunoreactivity
Although these drugs did not change the ME-I in the frontal cortex, ME-I significantly decreased in the limbic brain area and the striatum. And that in the hippocampus reversely increased with CLO or MIA.
(3) Opioid receptor bindings
Chronic treatment with IMI, CLO, MIA commonly resulted in decreases of <mu>-type and <deta>-type opioid receptor binding, as well as decrease of ME-I in the limbic brain area and the striatum in part. These finding shows the hypoactivity of opioid system in these brain areas following chronic antidepressants treatment. The hypothesis that the byperactivity of the opioid systems in these brain regions in depression might be supported by our findings.
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