title: Changes in cortical beta-adrenergic receptor density and neuronal sensitivity to norepinephrine accompany morphine dependence and withdrawal.
abstract: 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.
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D008297:Male; D009021:Morphine Dependence / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
chemical_list: D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine