McDonald C G, Eppolito A K, Brielmaier J M, Smith L N, Bergstrom H C, Lawhead M R, Smith R F
Department of Psychology, George Mason University, MS 3F5, Fairfax, VA 22030, USA.
Brain Res. 2007 Jun 2;1151:211-8. doi: 10.1016/j.brainres.2007.03.019. Epub 2007 Mar 12.
Male Long-Evans rats were administered nicotine bitartrate or sodium tartrate either during adolescence (p29-43) or adulthood (p80-94). Route of administration was via subcutaneously implanted osmotic pump (initial dose 2.0 mg/kg/day, free base). Five weeks following nicotine administration, brains were processed for Golgi-Cox staining. Medium spiny neurons from nucleus accumbens (NAc) shell were digitally reconstructed for morphometric analysis. Total dendritic length and branch number were greater in medium spiny neurons from animals pretreated with nicotine during adolescence. A branch order analysis indicated that increased branch number was specific to higher order branches. Mean branch lengths did not differ with respect to treatment as a function of branch order. Thus, nicotine-induced increases in total dendritic length were a function of greater numbers of branches, not increased segment length. In contrast, adult nicotine exposure did not significantly alter total dendritic length or branch number of medium spiny neurons. Total dendritic length and branch number of a second morphological type, the large aspiny neuron, did not differ following either adolescent or adult pretreatment. The age-dependent alteration of accumbal structure was associated with qualitatively different behavioral responses to drug challenge. These data provide evidence that drug-induced structural plasticity in nucleus accumbens is considerably more pronounced during adolescence.
雄性Long-Evans大鼠在青春期(第29 - 43天)或成年期(第80 - 94天)接受酒石酸尼古丁或酒石酸钠处理。给药途径是通过皮下植入渗透泵(初始剂量2.0毫克/千克/天,游离碱)。尼古丁给药五周后,对大脑进行高尔基-考克斯染色处理。对伏隔核(NAc)壳中的中等棘状神经元进行数字重建以进行形态计量分析。青春期接受尼古丁预处理的动物的中等棘状神经元的总树突长度和分支数量更大。分支顺序分析表明,分支数量增加特定于高阶分支。平均分支长度在不同处理组之间,作为分支顺序的函数并无差异。因此,尼古丁诱导的总树突长度增加是分支数量增加的结果,而非节段长度增加。相比之下,成年期暴露于尼古丁并未显著改变中等棘状神经元的总树突长度或分支数量。第二种形态类型,即大型无棘神经元,在青春期或成年期预处理后,其总树突长度和分支数量并无差异。伏隔核结构的年龄依赖性改变与对药物激发的定性不同的行为反应相关。这些数据提供了证据,表明药物诱导的伏隔核结构可塑性在青春期更为明显。