Effect of chronic antidepressant treatment on responses to apomorphine in selectively bred rat strains

The purpose of this study was to verify the dopamine-sensitizing behavioral effect of chronic antidepressant treatment in two selectively bred rat strains: the hypercholinergic Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL). Two antidepressants, desipramine HCl (DMI) and sertraline HCl, were injected IP in separate groups of FSL and FRL rats in a dose of 16.5 mumol/kg twice daily for 16 days. Twenty-four hours after withdrawal, locomotor and hypothermic responses to 0.2 mg/kg of apomorphine, SC, were examined. Attenuation of the effect of apomorphine was observed in the open field: FRLs withdrawn from sertraline were significantly less mobile than control FRLs, and the same trend was found in FSL rats. Chronic DMI resulted in similar changes in the locomotor activity. Sertraline treatment decreased apomorphine-induced hypothermia by almost half in FSLs, whereas slight hyperthermia was induced in FRL rats instead. The present results suggest that in these selectively bred strains, a serotonergic antidepressant such as sertraline may have sensitized dopaminergic autoreceptors and/or desensitized postsynaptic receptors. Apomorphine-induced hypothermia could be mediated by serotonergic neuron function that may have been altered by chronic sertraline but not DMI treatment.