Ontogeny of dopamine, serotonin and spirodecanone receptors in rat forebrain--an autoradiographic study

Abstract

Sections from freshly frozen neonatal rat brain, ages 0-21 days, were incubated with [3H]spiperone (SP). Initial studies characterized the binding sites for SP in terms of association and dissociation rates, saturability and pharmacology. The binding sites were found to be predominantly dopamine D2 receptors in sections centered in the striatum and these receptors were similar to receptors in adult brain. Autoradiographic studies using in vitro techniques examined the anatomic distribution of [3H]SP binding sites. Using domperidone, ketanserin and (+)butaclamol it was possible to differentiate dopamine D2, serotonin S2 and spirodecanone receptors. Dopamine receptors were found at birth in striatum and nucleus accumbens and increased in density with age. In the first two weeks postnatally there was an apparent dorsolateral to ventromedial gradient in the striatum. Serotonin S2 receptors were found in the cortex, lateral olfactory tubercles and nucleus accumbens and claustrum. These receptors increased in density with age but to a much lesser extent than dopamine receptors. Spirodecanone receptors were first apparent in the piriform cortex by day 5. They became very dense with age in particular regions, i.e., layer II of cortex, piriform cortex, medial olfactory tubercles, lateral septum and in patches in the nucleus accumbens. These studies delineate with a high resolution at an anatomical level the major receptor sites for neuroleptic drugs in the developing rat forebrain. They describe the developmental pattern of these receptors and provide a basis for further studies on their control and function during development.