Effect of the endogenous κ opioid agonist dynorphin A(1-17) on cocaine-evoked increases in striatal dopamine levels and cocaine-induced place preference in C57BL/6J mice

被引:92
作者
Zhang, Y [1 ]
Butelman, ER [1 ]
Schlussman, SD [1 ]
Ho, A [1 ]
Kreek, MJ [1 ]
机构
[1] Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10021 USA
关键词
dynorphin A (1-17); cocaine; microdialysis; dopamine; conditioned place preference; endogenous kappa opioid agonist;
D O I
10.1007/s00213-003-1688-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Rationale. Effects of synthetic kappa opioid receptor agonists on cocaine-induced reward have been studied extensively in rats but relatively few studies have used the endogenous kappa agonist dynorphin A(1-17). Objectives. Three studies were conducted to examine the effect of the natural sequence dynorphin on cocaine-induced increases in dopamine, on the formation of conditioned place preference and on increases in locomotor activity in C57BL/6 J mice. Methods. After implantation of guide cannulae into the caudate putamen, mice were allowed 4-5 days to recover from surgery. In the first study, dynorphin A (0, 1, 2, 4.4 nmol) was infused into the caudate putamen and dopamine levels were measured by in vivo microdialysis in that brain region. Then, the effect of dynorphin A (4.4 nmol) on increases in dopamine levels induced by 15 mg/kg cocaine i.p. was also measured with in vivo microdialysis. The third experiment examined the effect of dynorphin A (4.4 nmol) on conditioned place preference and locomotion induced by 15 mg/kg cocaine. Results. Dynorphin A significantly decreased basal dopamine levels in a dose-dependent manner by more than 60% at the highest dose, and this effect was completely blocked by pre-injection of the kappa-opioid receptor antagonist nor-BNI (10 mg/kg). The highest dose of dynorphin (4.4 nmol) blocked increases in dopamine levels, the formation of conditioned place preference and attenuated locomotion induced by 15 mg/kg cocaine. Conclusion. The blockade of the cocaine-induced rise in striatal dopamine may contribute to both dynorphin's ability to prevent the development of cocaine-induced conditioned place preference and to attenuate the increase in locomotor activity.
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页码:422 / 429
页数:8
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