Schramm-Sapyta Nicole L, Olsen Christopher M, Winder Danny G
Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA.
Neuropsychopharmacology. 2006 Jul;31(7):1444-51. doi: 10.1038/sj.npp.1300918. Epub 2005 Oct 5.
Drugs of abuse affect behavior by altering neuronal communication within the brain. Previous research examining the effects of intraperitoneally administered cocaine has revealed that cocaine alters excitatory glutamatergic signaling, both directly through regulation of synaptic function, and indirectly through regulation of cellular excitability in areas of the drug reward circuitry such as the nucleus accumbens (NAcc) and ventral tegmental area. We have now extended these findings by testing the hypothesis that self-administration of cocaine might elicit similar alterations in excitatory signaling in the NAcc shell. We observed that cocaine self-administration reduces synaptically evoked excitatory responses recorded extracellularly in the NAcc shell compared to saline self-administration. This alteration was not accompanied by alterations in paired pulse ratio of synaptically evoked responses or in potentiation of these responses by application of the adenylyl cyclase activator forskolin. This reduction in glutamatergic signaling may be one mechanism by which cocaine exerts its long-term behavioral effects.
滥用药物通过改变大脑内的神经元通讯来影响行为。先前研究腹腔注射可卡因的效果时发现，可卡因会改变兴奋性谷氨酸能信号传导，既直接通过调节突触功能，也间接通过调节药物奖赏回路区域（如伏隔核和腹侧被盖区）的细胞兴奋性。我们现在通过测试可卡因自我给药可能会在伏隔核壳层引发类似兴奋性信号改变这一假设，扩展了这些发现。我们观察到，与生理盐水自我给药相比，可卡因自我给药会降低在伏隔核壳层细胞外记录到的突触诱发兴奋性反应。这种改变并未伴随突触诱发反应的配对脉冲比率变化，也未因应用腺苷酸环化酶激活剂福斯高林而使这些反应增强。谷氨酸能信号传导的这种降低可能是可卡因发挥其长期行为效应的一种机制。
