CHRONIC DESIPRAMINE TREATMENT REDUCES REGIONAL NEUROPEPTIDE-Y BINDING TO Y2-TYPE RECEPTORS IN RAT-BRAIN

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 [H-3]proprionyl NPY to membranes prepared from frontal cortex, nucleus accumbens, hypothalamus and hippocampus. There was no change in binding of [H-3]proprionyl NPY in the parieto-occipital cortex, striatum or amygdala. Scatchard analysis of binding data from frontal cortical and hippocampal membranes showed that [H-3]proprionyl NPY bound to a single site with a K(d) of approximately 0.3 nM. The loss of [H-3]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-mu-M) 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 Y1 NPY-type receptors which are linked to the hydrolysis of inositol phospholipids. However, the ability of NPY (0.05-0.5-mu-M) to inhibit forskolin (1-mu-M) stimulated adenylate cyclase via Y2 NPY-type receptors in rat frontal cortical slices was significantly reduced following chronic desipramine treatment. This finding suggests that the reduction of [H-3]proprionyl NPY binding in selective brain regions may be the result of an antidepressant-induced loss of Y2-type NPY receptors which are negatively linked to adenylate cyclase.