Blockade of dopamine, but not noradrenaline, transporters produces hyperthermia in rats that lack serotonin transporters

Eur J Pharmacol. 2010 Mar 10;629(1-3):7-11. doi: 10.1016/j.ejphar.2009.11.049. Epub 2009 Dec 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atomoxetine Hydrochloride
  • Body Temperature / drug effects
  • Bupropion / pharmacology
  • Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Fever / etiology
  • Fever / metabolism*
  • Fever / physiopathology
  • Injections / adverse effects
  • Male
  • Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors
  • Norepinephrine Plasma Membrane Transport Proteins / metabolism
  • Piperazines / pharmacology
  • Propylamines / pharmacology
  • Rats
  • Serotonin Plasma Membrane Transport Proteins / deficiency*
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Stress, Physiological

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Norepinephrine Plasma Membrane Transport Proteins
  • Piperazines
  • Propylamines
  • Serotonin Plasma Membrane Transport Proteins
  • Bupropion
  • Atomoxetine Hydrochloride
  • vanoxerine