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Long-term imipramine effects are prevented by NMDA receptor blockade

Authors
Journal
Brain Research
0006-8993
Publisher
Elsevier
Publication Date
Volume
606
Issue
1
Identifiers
DOI: 10.1016/0006-8993(93)91570-i
Keywords
  • Antidepressant
  • Adenylyl Cyclase
  • β-Adrenoceptor
  • Dopamine Receptor
  • Mk-801
  • Nmda Receptor
  • Quinpirole

Abstract

Abstract Long-term exposure to different antidepressant treatments induces increased motor response to central stimulants, due to a selective supersensitivity of dopamine D 2 receptors in the limbic areas. Such an effect is accompanied by down-regulation of dopamine D 1 receptor number, and by a decreased response of adenylyl cyclase to dopamine stimulation in the limbic system. Moreover, the number of β-adrenergic receptors and the response of adenylyl cyclase to β-adrenergic stimulation in the cortex result to be reduced. The present data confirms that imipramine (10 mg/kg twice a day for 3 weeks) produces such effects, and shows that the co-administration of imipramine with MK-801 (administered by a subcutaneously implanted minipump delivering 0.05 mg/kg/day of the compound) prevented the occurence of both the behavioral supersensitivity to quinpirole, and the decrease of dopamine D 1 and β-adrenergic receptor function.

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