Microinjection of MKª²801 into ventral tegmental area reduces naloxoneª²precipitated morphine withdrawal in rats

    WANG Huiª²Ling, ZHAO Yan, XIANG Xiaoª²Hui, WANG Huiª²Sheng

    Key Laboratory of Relation Gene to Environment & Diseases, Education Ministry,Department of Physiology, Medical College, Xi¬ðan Jiaotong University, Xi¬ðan 710061, China

    ¡¾Abstract¡¿ AIM: To study whether the blockade of glutamate NMDA receptors in the ventral tegmental area (VTA) modulates the morphine withdrawal in rats. METHODS: The effects of (+) MKª²801, microinjected unilaterally into the VTA 30 min before naloxone (2 mg/kg, ip) administration, on the morphine withdrawal were assessed. Morphine dependence developed with increasing morphine injection (ip) and morphine withdrawal was induced by injection (ip) of naloxone (2 mg/kg). Wet dog shakes and Gellertª²Holtzman score were used as the indexes to evaluate the intensity of morphine withdrawal. RESULTS: Unilateral microinjection of MKª²801 into the VTA significantly reduced the Gellertª²Holtzman score and the incidence of wet dog shakes in morphine withdrawal rats. CONCLUSION: MKª²801 (2, 5, 10 g/L) unilaterally administered into the VTA significantly reduces the intensity of morphine withdrawal syndrome in dependent rats. These data support that glutamatergic transmission in the VTA and its interactions with dopaminergic neurons in the mesolimbic system play some important roles in opiate withdrawal syndrome. Our findings also suggest a potential use of NMDA antagonists in the therapeutic treatment of opiate abuse. ......