This project seeks to determine the brainstem circuitry involved in the autonomic action of opiates during morphine tolerance/dependence and withdrawal. The approach to the problem is two pronged. First, to establish the sites of gene expression of the opiate peptides in the medulla of rats through the use of in situ hydridization and, with quantitative in situ hybridization, to determine how morphine tolerance/dependence and naloxone precipitated withdrawal affect mRNA production of opiate and other medullary neuropeptides. Second, to determine the role of the rostral ventral lateral medulla, nucleus of the solitary tract and the caudal ventral lateral medulla in the expression of the autonomic symptoms of morphine withdrawal through a series of acute physiological experiments in anesthetized rats previously made tolerant/dependent to morphine: a) by noting the effect of lesions in these medullary nuclei and in their projections to other brain areas on hemodynamic changes, sympathetic nerve activity and plasma vasopressin concentration during and following naloxone precipitated withdrawal, b) by determining if the autonomic symptoms of morphine withdrawal can be elicited by microinjections of naloxone into these brainstem areas, C) by recording identified cells (e.g. in RVL, cells identified as barosensitive, spinally projecting) in these cardiovascular medullary nuclei and noted activity changes during and following naloxone precipitated withdrawal.
