Hypersensitivity to noradrenaline in cortex after chronic morphine: relevance to tolerance and dependence

Abstract

OPIOID agents affect the activity of noradrenergic neurones in brain in the following ways: their firing rate recorded in the locus coeruleus is depressed1,2, noradrenaline (NA) levels or turnover is altered3 and the depolarisation-induced release of NA from cerebral slices is inhibited4,5. This latter effect suggests that opiate receptors responsible for an inhibition of noradrenergic transmission might be localised on noradrenergic neurones not only on the cell bodies6 but also on the nerve terminals. Because a sustained decrease in noradrenergic transmission in brain results in the development of hypersensitivity of target cells to NA7,8, it was of interest to assess the involvement of such a process in the long-term effects of opiates. We report here that opiate receptors are presynaptically localised on noradrenergic neurones as indicated by their depletion in cortex and cerebellum after a selective degeneration of these neurones, and that chronic treatment with morphine is followed by an increased responsiveness of the cortical cyclic AMP system to catecholamines, accompanied by an increased number of β-adrenergic receptors.