Effects of amantadine and budipine on antidepressant drug-evoked changes in extracellular 5-HT in the frontal cortex of freely moving rats

Owen, J.C.E. and Whitton, P.S. (2005) Effects of amantadine and budipine on antidepressant drug-evoked changes in extracellular 5-HT in the frontal cortex of freely moving rats. British Journal of Pharmacology, 145 (5). pp. 587-592. 10.1038/sj.bjp.0706188.

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DOI: 10.1038/sj.bjp.0706188

Abstract

1Evidence has recently suggested that NMDA receptors may play a role in the aetiology and possible treatment of depression and that weak noncompetitive NMDA receptor antagonists such as amantadine can synergize with conventional antidepressants in a model of the illness.2To try to obtain a neurochemical rationale for these findings, we have studied the effects of acute and chronic administration of amantadine or the related drug budipine on cortical release of 5-hydroxytryptamine (5-HT) following the antidepressants reboxitine (REB), paroxetine (PAROX) and clomipramine (CLOM) in freely moving rats by using microdialysis.3Acute administration of amantadine (40 mg kg−1), budipine (10 mg kg−1), REB (10 mg kg−1), PAROX (10 mg kg−1) or CLOM (10 mg kg−1) all failed to significantly alter extracellular 5-HT in the cortex. However, when either amantadine or budipine was administered 30 min prior to any of the three antidepressants, a significant rise in 5-HT was observed.4For chronic studies, the effects of the drugs were studied at 4, 7, 14 and 21 days. Amantadine and budipine did not significantly alter extracellular 5-HT at any time point. The three antidepressant drugs all elicited a gradual increase in 5-HT, which became significant after 14 days and tended to plateau thereafter. When either amantadine (20 mg kg−1) or budipine (5 mg kg−1) was coadministered with any of the three antidepressants, two differences were seen compared with the effects of the antidepressants alone. Firstly, the time required for significant increases in cortical 5-HT was reduced with elevated levels now being observed by 7 days. Secondly, the absolute magnitude of the increase in extracellular 5-HT was markedly greater in these rats from day 7 until the end of the experiment.5If, as is widely considered, an increase in extracellular 5-HT represents a critical step in the mechanism of action of antidepressants, these data suggest that combine

Item Type:Article
Uncontrolled Keywords:Antidepressants;amantadine;budipine;5-HT;cortex;microdialysis
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:3113
Journal or Publication Title:British Journal of Pharmacology
Deposited By:Library Staff
Deposited On:27 Apr 2012 10:53
Last Modified:27 Apr 2012 10:53

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