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.