Linked Life Data

18606402

Source:http://linkedlifedata.com/resource/pubmed/id/18606402

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2008-8-4
pubmed:abstractText
Disturbances in the serotonergic system are implicated in many central nervous system disorders. The serotonin transporter (SERT) regulates the serotonin homeostasis in the synapse. We recently developed a rat which lacks the serotonin transporter (SERT(-/-)). It is likely that adaptive changes take place at the level of pre- and postsynaptic 5-HT receptors. Because autonomic responses are often used to measure 5-HT(1A) receptor function, we analysed these responses by examining the effects of a 5-HT(1A) receptor agonist and antagonist under in vivo conditions in the SERT(-/-) rat. Moreover, we studied the effect of a mild stressor on the body temperature (stress-induced hyperthermia) because of the known involvement of 5-HT(1A) receptors in this phenomenon. Results show that core body temperature did not differ between genotypes under basal, non-stressed conditions. Compared to SERT(+/+) rats, stress-induced hyperthermia was reduced in SERT(-/-) rats. The 5-HT(1A) receptor agonist [R(+)-N-(2[4-(2,3-dihydro-2-2-hydroxy-methyl-1,4-benzodioxin-5-yl)-1-piperazininyl]ethyl)-4-fluorobenzoamide HCl (flesinoxan) reduced stress-induced hyperthermia in both genotypes. The flesinoxan-induced hypothermia in SERT(+/+) rats was blocked by the 5-HT(1A) receptor antagonist [N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl) cyclohexane carboxamide 3HCl (WAY100635). Moreover, WAY100635-induced hyperthermia in SERT(-/-), but not in SERT(+/+) rats. In SERT(-/-) rats, WAY100635 completely blocked the flesinoxan-induced reduction of stress-induced hyperthermia. Interestingly, flesinoxan-induced hypothermia was absent in SERT(-/-) rats. It is concluded that the SERT knockout rat reveals that 5-HT(1A) receptors modulating stress-induced hyperthermia belong to a population of receptors that differs from that involved in hypothermia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
590
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
190-7
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Stress-induced hyperthermia and basal body temperature are mediated by different 5-HT(1A) receptor populations: a study in SERT knockout rats.
pubmed:affiliation
Department Cognitive Neuroscience: Psychoneuropharmacology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. j.olivier@cns.umcn.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't