Chronic treatment with imipramine: further functional evidence for the enhanced noradrenergic transmission in flexor reflex activity.

The chronic administration of imipramine (IMI; 10 mg/kg orally, twice daily for 14 days) enhanced the flexor reflex of the hind limb in the spinal rat. This effect was maintained for at least 72 h after termination of drug administration. Phenoxybenzamine but not cyproheptadine abolished the enhanced activity of the flexor reflex. After chronic administration of IMI high levels of desipramine (DMI) were found in the spinal cord, whereas IMI was not detectable there. No correlation was found between the levels of DMI in the spinal cord and the enhancement of the flexor reflex amplitude. A single i.v. dose of DMI facilitated the flexor reflex for a short period of time. In rats treated chronically with IMI, the binding of 3H-prazosin, a ligand of alpha 1-adrenoceptors, to spinal cord tissue was increased. The present results are a further argument for the previously advanced hypothesis that chronic administration of antidepressant drugs leads to an enhanced noradrenergic transmission, probably by increasing the number of alpha 1-adrenoceptors.