Blockade of dopamine, but not noradrenaline, transporters produces hyperthermia in rats that lack serotonin transporters.
To investigate whether life-long disturbed serotonin neurotransmission may result in adaptive changes of dopaminergic and noradrenergic systems, effects of drugs on stress-induced hyperthermia were studied in serotonin transporter knockout rats. The noradrenalin transporter blocker atomoxetine was more effective in reducing stress-induced hyperthermia, induced by an injection, in serotonin transporter (SERT) knockout (SERT(-/-)) rats compared to SERT(+/+) rats. The dopamine transporter blocker GBR12909 increased the core body temperature in SERT(-/-) rats, and had no effect on the SERT(+/+) rats. Finally, the noradrenalin transporter together with dopamine transporter blocker bupropion was more effective in decreasing the stress of an injection in SERT(-/-) rats than in SERT(+/+) rats. These data suggest that the sensitivity of dopamine and noradrenalin receptors is changed in serotonin transporter knockout rats. The lack of the serotonin transporter in SERT(-/-) rats might reflect humans with a life-long disturbed serotonin system, making this rat a good model to study possible changes in dopaminergic and noradrenergic systems in psychiatric disorders.
Olivier
Jocelien D A
JD
Donders Institute for Brain, Cognition and Behaviour: Department of Cognitive Neuroscience: Molecular Neurobiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. j.olivier@cns.umcn.nl
Cools
Alexander R
AR
Deen
Peter M T
PM
Olivier
Berend
B
Ellenbroek
Bart A
BA
D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001831:Body Temperature / Q000187:drug effects; D016642:Bupropion / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005334:Fever / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007267:Injections / Q000009:adverse effects; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency* / Q000378:metabolism; D013312:Stress, Physiological
D050483:Dopamine Plasma Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines; D011437:Propylamines; D050486:Serotonin Plasma Membrane Transport Proteins; D016642:Bupropion; D000069445:Atomoxetine Hydrochloride; C043425:vanoxerine