Morphine Desensitization and Cellular Tolerance Are Distinguished in Rat Locus Ceruleus Neurons

Morphine desensitization and cellular tolerance are distinguished in rat locus ceruleus neurons.

μ-Opioid receptor desensitization is considered an initial step in the development of tolerance. Curiously, the commonly used opioid morphine produces robust tolerance but minimal acute desensitization. This study was designed to test the hypothesis that desensitization is indeed present in morphine-treated animals and is distinguished from cellular tolerance by time course of recovery and mech...

Morphine desensitization and cellular tolerance are distinguished in rat locus coeruleus neurons

Ethanol reversal of cellular tolerance to morphine in rat locus coeruleus neurons.

Consumption of ethanol is a considerable risk factor for death in heroin overdose. We sought to determine whether a mildly intoxicating concentration of ethanol could alter morphine tolerance at the cellular level. In rat locus coeruleus (LC) neurons, tolerance to morphine was reversed by acute exposure of the brain slice to ethanol (20 mM). Tolerance to the opioid peptide [d-Ala(2),N-MePhe(4),...

Role of protein kinase C and μ-opioid receptor (MOPr) desensitization in tolerance to morphine in rat locus coeruleus neurons

In morphine tolerance a key question that remains to be answered is whether mu-opioid receptor (MOPr) desensitization contributes to morphine tolerance, and if so by what cellular mechanisms. Here we demonstrate that MOPr desensitization can be observed in single rat brainstem locus coeruleus (LC) neurons following either prolonged (> 4 h) exposure to morphine in vitro or following treatment of...

Effect of reversible inactivation of locus ceruleus on naloxone-induced withdrawal syndrome in paragigantocellular neurons in morphine-dependent rats

In this study, the effect of reversible inactivation of locus ceruleus (LC) on naloxone- induced withdrawal syndrome in paragigantocellular (PGi) neurons in morphine- dependent rats was investigated. For inactivation of LC, 1 µl of lidocaine (2%) was used and for induction of withdrawal syndrome, naloxone hydrochloride (2 mg/kg) was injected systemically. The results showed that in dependent gr...