Acute desipramine treatment reduces regional serotonin synthesis rates, while chronic treatment elevates rates, in a rat model of depression: An autoradiographic study

It has been suggested that 5-HT (serotonin; 5-hydroxytryptamine) and/or the norepinephrine receptor adaptive processes in the brain are the basis for the efficacy of antidepressant treatments, including electro-convulsive shock therapy. In the present study, the effect of acute (10 mg/kg; i.p. injection) and chronic (10 mg/kg/day; delivered by subcutaneous mini-pump) desipramine treatments on regional 5-HT synthesis were evaluated in the Flinders Sensitive Line (FSL; “depressed” rats), as well as the control Flinders Resistant Line (FRL), of rats, using α-[14C]methyl-l-tryptophan autoradiography. The control rats in each of the strains received the same volume (volume in which drug was dissolved) of saline (whether through an injection or, in the case of the chronic experiments, via an osmotic mini-pump), while the treated rats received desipramine (DMI) dissolved in saline (again, as an i.p. injection or by osmotic mini-pump). The rats were randomly assigned to different groups. The results indicate that acute treatment produces a reduction in regional 5-HT synthesis in both the FSL and FRL rats, while chronic treatment produces an elevation of regional 5-HT synthesis in both strains, but the effect was somewhat greater in the FRL rats. When comparing these results to those of normal Sprague–Dawley rats, our results suggest that it is more informative to study 5-HT synthesis in an animal model of depression.

► Acutely desipramine treatment reduces serotonin synthesis in FSL and FRL rats.
► Chronically treated rats with desipramine show elevation of the regional serotonin synthesis.
► The increases in the regional synthesis are about the same in FRL and FSL rats.
► Neither acute or chronic treatment have effect on the plasma tryptophan concentration.