Inhibition of nitric oxide synthase in the ventral tegmental area attenuates cocaine sensitization in rats

被引:19
作者
Byrnes, JJ
Pantke, MM
Onton, JA
Hammer, RP
机构
[1] New England Med Ctr, Dept Psychiat, Boston, MA 02111 USA
[2] Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA
[3] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA
[4] Tufts Univ, Sch Med, Dept Psychiat, Boston, MA 02111 USA
关键词
behavioral sensitization; cocaine; nitric oxide synthase; 7-nitroindazole; ventral tegmental area;
D O I
10.1016/S0278-5846(99)00094-9
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
1. Male Sprague-Dawley rats were pretreated via bilateral infusion of the VTA with the selective neuronal nitric oxide synthase inhibitor, 7-nitroindazole (0, 8, or 40 ng/hemisphere), prior to each of 7 daily systemic cocaine (30 mg/kg, i.p.) or saline (1 ml/kg) treatments. 2. After a 7-day treatment withdrawal period, rats received a final systemic challenge with either cocaine (30 mg/kg, i.p.) or saline (1 ml/kg). 3. Locomotor and stereotypic activity were measured following the first and last treatments. 4. Daily cocaine treatment led to the development of sensitization to its stereotypic effects as revealed upon drug challenge. 5. The development of sensitization of cocaine-induced stereotypy was completely blocked by daily intra-VTA pretreatment with 7-nitroindazole. 6. In addition, attenuation of the locomotor effects of cocaine challenge was also observed in animals that received daily intra-VTA 7-nitroindazole (40 ng/hemisphere) infusions. 7. The results indicate that VTA nitric oxide is necessary for the development of sensitization of cocaine-induced stereotypic behavior, and that its repeated inhibition may produce lasting effects on the locomotor response to the drug.
引用
收藏
页码:261 / 273
页数:13
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