Schroeder Joseph A, Niculescu Michelle, Unterwald Ellen M
Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Synapse. 2003 Jan;47(1):26-32. doi: 10.1002/syn.10148.
Chronic cocaine administration produces alterations in mu and kappa opioid receptor density as well as striatal and accumbens opioid-regulated adenylyl cyclase activity, suggesting a psychostimulant responsive interaction between opioidergic and dopaminergic systems. Stimulation of G-protein-coupled opioid receptors inhibits adenylyl cyclase production of cyclic AMP. The present study employed in situ [(35)S]GTPgammaS binding to measure opioid receptor-stimulated activation of G-proteins in response to acute and chronic cocaine exposure. Male Fischer rats received acute (1 or 3 days) or chronic (14 days) binge pattern cocaine administration. Three and 14 days of cocaine injections resulted in greater increases in the ability of the mu receptor agonist DAMGO to stimulate [(35)S]GTPgammaS binding in both the core and the shell of the nucleus accumbens, all regions of the caudate putamen and the cingulate cortex compared with saline-matched controls. The greatest increases in DAMGO-stimulated [(35)S]GTPgammaS binding were observed in the dorsal areas of the caudate putamen in animals that received 14 days of cocaine. No significant changes in delta (DPDPE), or kappa (dynorphin A(1-17)) receptor-stimulated [(35)S]GTPgammaS binding were found in any brain region in response to cocaine administration. These results demonstrate that binge pattern cocaine administration induce changes in mu but not delta or kappa opioid receptor-mediated G-protein activity. This study provides support for the hypothesis that the addictive properties of both psychostimulants and opiates may share common neurochemical signaling substrates.
长期给予可卡因会导致μ和κ阿片受体密度以及纹状体和伏隔核中阿片调节的腺苷酸环化酶活性发生改变，这表明阿片能系统和多巴胺能系统之间存在对精神兴奋剂有反应的相互作用。刺激G蛋白偶联的阿片受体会抑制腺苷酸环化酶产生环磷酸腺苷。本研究采用原位[(35)S]GTPγS结合法来测量急性和慢性可卡因暴露后阿片受体刺激的G蛋白激活情况。雄性Fischer大鼠接受急性（1或3天）或慢性（14天）的暴饮暴食式可卡因给药。与生理盐水匹配的对照组相比，注射3天和14天可卡因后，μ受体激动剂DAMGO刺激伏隔核核心和壳层、尾壳核所有区域以及扣带回皮质中[(35)S]GTPγS结合的能力有更大程度的增加。在接受14天可卡因注射的动物中，尾壳核背侧区域观察到DAMGO刺激的[(35)S]GTPγS结合增加最为显著。在任何脑区，给予可卡因后，δ（DPDPE）或κ（强啡肽A(1-17)）受体刺激的[(35)S]GTPγS结合均未发现显著变化。这些结果表明，暴饮暴食式可卡因给药会诱导μ阿片受体介导的G蛋白活性发生变化，但不会诱导δ或κ阿片受体介导的G蛋白活性发生变化。本研究为精神兴奋剂和阿片类药物的成瘾特性可能共享共同神经化学信号底物这一假说提供了支持。
