Changes in cortical beta-adrenergic receptor density and neuronal sensitivity to norepinephrine accompany morphine dependence and withdrawal.

Radioligand binding experiments were carried out in conjunction with electrophysiological recordings in vivo in the parietal cortex in rats to assess changes in postsynaptic beta-adrenergic receptor function that result after chronic administration of morphine and during morphine withdrawal. Chronic treatment of rats with morphine for 14 days resulted in a 38% increase in the density of beta-adrenergic receptors in the parietal cortex, as measured by the binding of the specific antagonist [3H]dihydroalprenolol (DHA). In comparison, following withdrawal in the chronic morphine-treated animals, the number of specific [3H]DHA binding sites in this same cortical region was decreased 25%, when compared to saline-treated controls. These alterations in cortical beta-adrenergic receptor density were not accompanied by a significant change in the dissociation constant (Kd) for [3H]DHA or in the inhibitory constants (Ki) for the specific agonists norepinephrine and isoproterenol. Microiontophoretic testing revealed that the changes in beta-adrenergic receptor density found in parietal cortex after chronic morphine treatment and during morphine withdrawal were accompanied by a selective increase and decrease, respectively, in the sensitivity of cerebrocortical neurons in the same region to beta-adrenergic stimulation. These results suggest that changes in central adrenergic function might be related to the formation and/or expression of dependence on morphine.