Reduced [125I]-Bolton Hunter substance P binding (NK1 receptors) in the basal forebrain nuclei of aged rats

1. Quantitative autoradiography and homogenate radioligand binding of [125I]-Bolton Hunter substance P ([125I]-BHSP) were used to compare brain NK1 receptors in young (2 months) and aged (18-20 months) rats. 2. The autoradiographic distribution and density of [125I]-BHSP binding sites was similar in all cortical regions of young and aged rats. In contrast, the density of [125I]-BHSP binding sites was significantly (P < 0.05) lower in the basal forebrain nuclei (intermediate part of the lateral septal nuclei, medial septal nucleus and horizontal and vertical nuclei of the diagonal band) of aged rats. In all other brain regions examined, binding densities were almost identical in young and aged rats. 3. Because a population of NK1 receptors ([125I]-BHSP binding sites) in the basal forebrain nuclei is associated with cholinergic neurons, the decrease in NK1 receptors in aged rats may reflect degeneration of cholinergic neurons and contribute to the motor and cognitive deficiencies that occur with ageing.