Quantification of 5-hydroxytryptamine 1a receptors in the cerebellum of normal and X-irradiated rats during postnatal development

Abstract

5-Hydroxytryptamine 1A receptors were studied in rats during the first postnatal month in the normal cerebellum and in the granule cell-deprived cerebellum produced by X-irradiation at postnatal day 5. Quantitive autoradiographic studies on sagittal sections of cerebellar vermis, using [ 125I]BH-8-MeO-N-PAT as radioligand or specific anti-receptor antibodies, revealed that 5-hydroxytryptamine 1A receptors existed in the molecular/Purkinje cell layer but at variable density from one lobule to another. Thus, in both normal and X-irradiated rats, the posterior lobules were more heavily labelled than the anterior ones, and the density of 5-hydroxytryptamine 1A sites decreased progressively in all the cerebellar folia down to hardly detectable levels at postnatal day 21. However, the intensity of labelling remained higher at postnatal day 8 and postnatal day 12 in X-irradiated rats than in age-paired controls. Measurements of [ 3H]8-OH-DPAT specific binding to membranes from whole cerebellum confirmed that the density of 5-hydroxytryptamine 1A sites per mg membrane protein (B max) was higher in X-irradiated animals than in age-paired controls. However, on a “per cerebellum” basis, no significant difference could be detected between the total number of 5-hydroxytryptamine 1A sites, which progressively increased in both control and X-irradiated animals during the first postnatal month. These results therefore show that 5-hydroxytryptamine 1A receptors are not located on developing granule cells. The progressive decrease in 5-hydroxytryptamine 1A receptor density during the first postnatal month did not reflect a transient expression of 5-hydroxytryptamine 1A receptors in the cerebellum of newborn rats, but resulted from the progressive “dilution” of these sites in this growing structure. The higher density of 5-hydroxytryptamine 1A sites in X-irradiated rats simply reflected a lower “dilution” due to the delayed growth of the cerebellum in these animals.