Naloxone-precipitated withdrawal enhances ERK phosphorylation in prefrontal association cortex and accumbens nucleus of morphine-dependent mice

• Published in: Neuroscience letters Vol. 468; no. 3; pp. 348 - 352
• Main Authors: Li, Tao, Hou, Ying, Cao, Wei, Yan, Chun-xia, Chen, Teng, Li, Sheng-bing
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 14.01.2010; Elsevier
• Subjects: Accumbens nucleus (Acb); Analgesics; Animals; Biological and medical sciences; Caudate putamen (CPu); Dependence; Extracellular Signal-Regulated MAP Kinases - metabolism; Frontal association cortex (FrA); Fundamental and applied biological sciences. Psychology; Male; MAPK pathway; Medical sciences; Mice; Mice, Inbred C57BL; Morphine; Morphine - adverse effects; Morphine Dependence - metabolism; Morphine Dependence - psychology; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; Neuropharmacology; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Pharmacology. Drug treatments; Phosphorylation; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Putamen - metabolism; Substance Withdrawal Syndrome - metabolism; Substance Withdrawal Syndrome - psychology; Vertebrates: nervous system and sense organs; Withdrawal syndrome; MAPK pathway; Caudate putamen (CPu); Frontal association cortex (FrA); Dependence; Morphine; Withdrawal syndrome; Accumbens nucleus (Acb); Phosphorylation; Extracellular signal-regulated protein kinase; Central nervous system; Opiates; Frontal cortex; Narcotic analgesic; Encephalon; Enzyme; Transferases; Rodentia; Mitogen-activated protein kinase; Basal ganglion; Prefrontal cortex; Putamen; Nucleus accumbens; Vertebrata; Mammalia; Naloxone; Mouse; Animal
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2009.11.030

Mitogen-activated protein kinases (MAPK) can be activated by opioids such as morphine via opioid receptor, and their activations have been observed in synaptic plasticity, learning, memory and addiction. Long-term exposure to morphine may induce physical dependence, manifested as somatic withdrawal symptoms such as diarrhea, body weight loss, jumping and headshaking, when drug is deprived. Though morphine dependence and withdrawal have been extensively studied, their molecular mechanisms have not been fully elucidated. In the present study, the physical dependence on morphine was developed in mice by an intermittent, escalating procedure of morphine injections, and was measured by the body weight loss and the behavioral signs (jumping and headshaking). We found that the mice with chronic morphine administration experienced dramatic body weight loss, compared with the saline-treated controls. Naloxone-precipitated withdrawal led to more body weight loss, compared with spontaneous withdrawal. Naloxone-precipitated withdrawal mice showed significantly aggravated morphine-withdrawal symptoms (including jumping and heading shaking), compared with spontaneous withdrawal mice. MAPK pathway activities in the frontal association cortex (FrA), accumbens nucleus (Acb) and caudate putamen (CPu) were examined to probe into molecular mechanism for morphine dependence and withdrawal. Compared with saline-treated mice, morphine-dependent mice and spontaneous withdrawal mice, naloxone-precipitated withdrawal mice showed a significantly increased ERK phosphorylation in FrA and Acb, but not in CPu. However, the activities of other protein kinases in the MAPK pathway, including p38 and JNK, showed no changes in FrA, Acb and CPu of the mice during the chronic morphine dependence and withdrawal phases. These results suggest that the ERK phosphorylation in FrA and Acb may be associated with naloxone-precipitated withdrawal syndrome.