[The mechanisms of morphine dependence and it's withdrawal syndrome: study in mutant mice].
To investigate the involvement of catecholamines and/or the cyclic AMP (cAMP) systems in the development of drug dependence, we examined whether morphine dependence was developed in tyrosine hydroxylase (TH) heterozygous (TH+/-) and cAMP response element binding protein (CREB) binding protein (CBP) heterozygous (CBP+/-) mice. Morphine (10 mg/kg) induced place preference in the wild-type mice. In the TH+/- and CBP+/- mice, however, we could not find any morphine-induced place preference. When the wild-type mice pretreated with morphine (10 mg/kg) twice a day for 5 days were challenged with naloxone (5 mg/kg), they showed increased numbers of jumping, rearing and forepaw tremor as a sign of withdrawal symptom and increased level of cAMP in the thalamus/hypothalamus, but not in the striatum. However, increased numbers of jumping and forepaw tremor in the TH+/- and CBP+/- mice and increased level of cAMP in the thalamus/hypothalamus of TH+/- mice were not observed. These results suggest that catecholamines and CBP are involved in the development of morphine dependence, and that some changes in the catecholaminergic and/or cAMP system induced by repeated morphine treatment play an important role in the addiction of morphine.
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65, Tsuruma-cho, Showaku, Nagoya 466-8560, Japan. y-noda@med.nagoya-u.ac.jp
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Noda
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Mamiya
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Nabeshima
D000818:Animals; D001921:Brain / Q000378:metabolism; D002395:Catecholamines / Q000096:biosynthesis / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000209:etiology*; D015398:Signal Transduction / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000209:etiology*
D002395:Catecholamines; D017362:Cyclic AMP Response Element-Binding Protein; D009020:Morphine; D000242:Cyclic AMP