Chronic desipramine treatment reduces regional neuropeptide Y binding to Y 2-type receptors in rat brain

Abstract

Chronic treatment of rats with desipramine and imipramine (5 mg/kg/twice daily/i.p.) for 14 days caused a significant reduction in the binding of [ 3H]proprionyl NPY to membranes prepared from frontal cortex, nucleus accumbens, hypothalamus and hippocampus. There was no change in binding of [ 3H]proprionyl NPY in the parieto-occipital cortex, striatum or amygdala. Scatchard analysis of binding data from frontal cortical and hippocampal membranes showed that [ 3H]proprionyl NPY bound to a single site with aK d of approximately 0.3 nM. The loss of [ 3H]proprionyl NPY binding in hippocampal and frontal cortical membranes revealed that chronic tricyclic antidepressant treatment produced a reduction in the number of binding sites with no change in the affinity for the ligand. Chronic desipramine treatment did not alter the ability of NPY (0.01–25 μM) to stimulate inositol phosphate accumulation in rat frontal cortical slices as compared to saline-treated animals. The lack of change of NPY-induced inositol phosphate accumulation following chronic desipramine treatment showed that there was no change to Y 1 NPY-type receptors which are linked to the hydrolysis of inositol phospholipids. However, the ability of NPY (0.05–0.5 μM) to inhibit forskolin (1 μM) stimulated adenylate cyclase via Y 2 NPY-type receptors in rat frontal cortical slices was significantly reduced following chronic desipramine treatment. This finding suggests that the reduction of [ 3H]proprionyl NPY binding in selective brain regions may be the result of an antidepressant-induced loss of Y 2-type NPY receptors which are negatively linked to adenylate cyclase.