Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Mignon, L. et al.

Postsynaptic 5-HT(1A) receptors mediate an increase in locomotor activity in the monoamine-depleted rat.

RATIONALE: In animal models of reduced dopamine transmission, such as haloperidol-induced catalepsy or monoamine-depleted animals, serotonin (5-hydroxytryptamine; 5-HT) 5-HT(1A) agonists appear to enhance motor activity. However, the exact mechanism remains unclear. OBJECTIVE: The objective of the present study was to demonstrate that 5-HT(1A) agonists can increase locomotor activity by activation of postsynaptic 5-HT(1A) heteroreceptors without the involvement of somatodendritic 5-HT(1A) autoreceptors which are known to regulate 5-HT neuronal activity. METHODS: The effects of the 5-HT(1A) full agonist R-(+)-8-hydroxy-2-(di- n-propylamino)tertralin ( R-(+)-8-OHDPAT) on locomotor activity in reserpinized (i.e., monoamine-depleted) rats were studied. RESULTS: The present data demonstrate that R-(+)-8-OHDPAT significantly increased locomotor activity in monoamine-depleted animals at a dose as low as 0.01 mg/kg. The partial 5-HT(1A) agonist/D(2) antagonist buspirone (3 mg/kg) also elevated locomotor activity. The effects of these 5-HT(1A) compounds were found to be similar to the locomotor-stimulating effect of the dopamine precursor 3,4-dihydroxyphenylalanine (150 mg/kg, 15 min after 50 mg/kg benserazide). The 5-HT(1A) antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide maleate (WAY 100635; 0.2 mg/kg) blocked the R-(+)-8-OHDPAT (0.03 mg/kg)-mediated increase in locomotion. Blockade of 5-HT synthesis with DL- p-chlorophenylalanine (pCPA), a tryptophan hydroxylase inhibitor, prior to reserpinization did not affect R-(+)-8-OHDPAT-induced locomotion. CONCLUSIONS: The present data indicate that R-(+)-8-OHDPAT can increase motor activity in monoamine-depleted rats through postsynaptic 5-HT(1A) receptors and not necessarily through 5-HT(1A) autoreceptor-mediated alterations in 5-HT synthesis and release. A potential mechanism of 5-HT(1A)-mediated modulation of non-monoaminergic motor circuits in the brain is discussed. Taken together, the results suggest that 5-HT(1A) agonists would provide a novel approach to the amelioration of antipsychotic-induced side effects and the symptomatic treatment of Parkinson's disease.[1]

References

Postsynaptic 5-HT(1A) receptors mediate an increase in locomotor activity in the monoamine-depleted rat. Mignon, L., Wolf, W.A. Psychopharmacology (Berl.) (2002) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.