Proenkephalin gene expression during rat basal ganglia development and the effects of chronic morphine exposure
Description
Proenkephalin is one of the three genes known to encode endogenous opioid peptides. An antibody directed against a unique peptide sequence within proenkephalin that is not found in any other known peptide sequence was characterized and compared to a methionine enkephalin antibody. This antibody was found to be specific for enkephalinergic cell bodies, fibers and terminals. The development of proenkephalin mRNA in the neostriatum and its derivative peptides in the globus pallidus were found to parallel neurogenetic gradients. Expression was also found early in the central nucleus of the amygdala, late in the nucleus accumbens and olfactory tubercle, and transiently in clusters within the neostriatum. Dopaminergic innervation was found to precede proenkephalin expression in the rostral neostriatum and to follow proenkephalin expression in the caudal neostriatum. Neostriatal cells becoming postmitotic on embryonic day 14 (E14) moved twice during the course of their development: first ventrolaterally and then later dorsomedially in clusters. In contrast, neurons born at E19 were found to migrate only ventrolaterally. Clusters of neurons born at E14 corresponded to substance P immunoreactive patches. At progressively more rostral levels, progressively fewer E14-generated cells were detected in the neostriatum. The development of the two main peptidergic projection neurons of the neostriatum, enkephalin and substance P, began from opposite poles of the neostriatum and adjacent structures of the extended amygdala. During the perinatal period (from E16 to the day of birth), the distribution of neurons expressing proenkephalin spread primarily dorsomedially and rostrally. In contrast, neurons expressing substance P spread primarily dorsomedially and caudally. By the day of birth, there was extensive overlap in the distributions of proenkephalin and substance P in the neostriatum, but little to no coexpression of both peptides was ever found. Chronic opiate exposure in utero resulted in a selective increase in proenkephalin mRNA expression in the patch compartment of the neostriatum. Similarities in the anatomical connections, neurochemistry and development of the extended amygdala and the neostriatal patch compartment suggest that they may form a fundamental forebrain circuitry involved in motivated behavior and fight or flight responses