Todtenkopf M S, Stellar J R, Williams E A, Zahm D S
Behavioral Genetics Laboratory, Department of Psychiatry, Harvard Medical School, McLean Hospital, MRC 001, 115 Mill Street, Belmont, MA 02478, USA.
Neuroscience. 2004;127(1):35-42. doi: 10.1016/j.neuroscience.2004.04.054.
Intermittent administration of psychostimulants such as cocaine and amphetamine can result in behavioral sensitization, which is believed to model the onset of drug addiction, as well as possible neural adaptations that lead to addictive behaviors. The dorsal striatum and the nucleus accumbens (NAc) have been shown to play an integral role in this phenomenon. However, these structures comprise a complex neuroanatomical organization, and few studies have correlated anatomical differentiation within these brain regions with functional (i.e. behavioral) outcome, particularly after psychostimulant exposure. Parvalbumin (PV)-containing GABAergic interneurons are a key neuronal cell population that can significantly regulate input-output functions in these brain regions. The present study quantified parvalbumin-immunoreactive cells in subterritories of the striatum and NAc in animals behaviorally sensitized to cocaine. Rats received a sensitization-inducing regimen of cocaine (twice-daily injections of 15 mg/kg i.p. for 5 consecutive days). Two or 14 days following the last injection, rats were given a challenge injection of cocaine (15 mg/kg i.p.), and killed 2 h later. Sections through the striatum (including the NAc) were processed for parvalbumin immunoreactivity, and the number of immunoreactive neurons was quantified. Repeated cocaine administration resulted in robust sensitization that correlated with transient increases in the number of PV immunoreactive neurons in the ventrolateral, dorsolateral and dorsomedial striatum. After a 2-week withdrawal period, sensitized animals showed a significant decrease in the number of PV+ neurons in the ventrolateral shell of the NAc and dorsomedial striatum, and no significant difference in any other area examined. These data suggest a dichotomous role for PV interneurons in different subterritories of the striatum and NAc during the short-term (induction) vs. long-term (expression) phases of cocaine sensitization.
间歇性给予可卡因和苯丙胺等精神兴奋剂会导致行为敏化，人们认为这模拟了药物成瘾的起始过程，以及可能导致成瘾行为的神经适应性变化。背侧纹状体和伏隔核在这一现象中已被证明起着不可或缺的作用。然而，这些结构包含复杂的神经解剖组织，很少有研究将这些脑区内的解剖学差异与功能（即行为）结果联系起来，尤其是在精神兴奋剂暴露之后。含小白蛋白（PV）的γ-氨基丁酸能中间神经元是一类关键的神经元细胞群体，可显著调节这些脑区的输入-输出功能。本研究对行为上对可卡因敏感的动物纹状体和伏隔核亚区域中含小白蛋白免疫反应性的细胞进行了定量。大鼠接受诱导可卡因敏感化的方案（连续5天每天两次腹腔注射15mg/kg）。在最后一次注射后的2天或14天，给大鼠腹腔注射一次激发剂量的可卡因（15mg/kg），并在2小时后处死。对穿过纹状体（包括伏隔核）的切片进行小白蛋白免疫反应性处理，并对免疫反应性神经元的数量进行定量。重复给予可卡因导致强烈的敏感化，这与腹外侧、背外侧和背内侧纹状体中PV免疫反应性神经元数量的短暂增加相关。在2周的戒断期后，敏感化动物伏隔核腹外侧壳和背内侧纹状体中PV+神经元的数量显著减少，而在其他任何检查区域均无显著差异。这些数据表明，在可卡因敏感化的短期（诱导）与长期（表达）阶段，PV中间神经元在纹状体和伏隔核的不同亚区域中发挥着双重作用。
