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Long-term imipramine effects are prevented by NMDA receptor blockade
M G De Montis1, C Gambarana, D Meloni
1Institute of Pharmacology, University of Siena, Italy.
Brain Research
|March 19, 1993
Summary
Antidepressant treatment with imipramine can cause behavioral changes by altering dopamine D2 and D1 receptors. Co-administering MK-801 with imipramine prevented these changes, suggesting a protective effect on neurotransmitter receptor function.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- Long-term antidepressant use can lead to altered dopamine D2 receptor supersensitivity and reduced dopamine D1 and beta-adrenergic receptor function.
- These neurochemical changes are associated with behavioral modifications in response to central stimulants.
Purpose of the Study:
- To investigate the effects of imipramine on dopamine and beta-adrenergic receptor systems.
- To determine if MK-801 can prevent the neurochemical and behavioral alterations induced by imipramine.
Main Methods:
- Rats were treated with imipramine (10 mg/kg twice daily for 3 weeks).
- MK-801 was co-administered via osmotic minipump (0.05 mg/kg/day).
- Behavioral supersensitivity to quinpirole and dopamine D1/beta-adrenergic receptor function were assessed.
Main Results:
- Imipramine treatment confirmed the induction of behavioral supersensitivity to quinpirole.
- Imipramine also caused a decrease in dopamine D1 and beta-adrenergic receptor function.
- Co-administration of imipramine and MK-801 prevented both the behavioral supersensitivity and the receptor function deficits.
Conclusions:
- Imipramine induces significant changes in dopamine and adrenergic receptor systems, leading to behavioral supersensitivity.
- MK-801 effectively counteracts the detrimental effects of imipramine on these receptor systems.
- This suggests a potential therapeutic strategy for mitigating side effects of long-term antidepressant treatment.