Sepúlveda Jacqueline, Oliva Patricio, Contreras Enrique
Departamento de Farmacología, Facultad de Ciencias Biológicas, Universidad de Concepción, P.O. Box 160-C, Concepción, Chile.
Eur J Pharmacol. 2004 Jan 12;483(2-3):249-58. doi: 10.1016/j.ejphar.2003.10.037.
The effects of discontinuing a chronic morphine treatment on the concentrations of glutamate and aspartate were analyzed in the nucleus accumbens of unrestrained unanesthetized rats. The administration of naloxone or the cessation of morphine administration resulted in increased concentrations of glutamate and aspartate in this central nervous system area. These increased amino acid concentrations were observed a few minutes after naloxone administration and persisted in the controls 48 h after the last dose of the opiate. Morphine withdrawal was also studied in rats not injected with naloxone. In these latter animals, increased concentrations of glutamate and aspartate persisted in controls 96 h after the last dose of the opiate. Single doses of morphine, acamprosate or riluzole administered to rats previously withdrawn from chronic morphine treatment restored the amino acid concentrations to normal levels. These results suggest that the maintenance of increased levels of amino acids could be the expression of new adjustments in central nervous system neurotransmission after discontinuation of the chronic morphine treatment.
在未麻醉的自由活动大鼠的伏隔核中，分析了停止长期吗啡治疗对谷氨酸和天冬氨酸浓度的影响。给予纳洛酮或停止吗啡给药会导致该中枢神经系统区域中谷氨酸和天冬氨酸的浓度升高。在给予纳洛酮几分钟后就观察到这些氨基酸浓度升高，并且在末次给予阿片类药物48小时后，对照组中仍然持续存在。还对未注射纳洛酮的大鼠进行了吗啡戒断研究。在这些后期动物中，末次给予阿片类药物96小时后，对照组中谷氨酸和天冬氨酸的浓度仍然持续升高。对先前已停止长期吗啡治疗的大鼠给予单剂量的吗啡、阿坎酸或利鲁唑，可使氨基酸浓度恢复到正常水平。这些结果表明，氨基酸水平升高的持续存在可能是长期吗啡治疗停止后中枢神经系统神经传递新调整的表现。
