Department of Neurobiology and Anatomy, The University of Texas, Medical School at Houston, Houston, TX 77030, USA.
Brain Res Bull. 2012 Mar 10;87(4-5):445-56. doi: 10.1016/j.brainresbull.2012.01.004. Epub 2012 Jan 13.
Methylphenidate (MPD) is a psychostimulant that enhances dopaminergic neurotransmission in the central nervous system by using mechanisms similar to cocaine and amphetamine. The mode of action of brain circuitry responsible for an animal's neuronal response to MPD is not fully understood. The nucleus accumbens (NAc) has been implicated in regulating the rewarding effects of psychostimulants. The present study used permanently implanted microelectrodes to investigate the acute and chronic effects of MPD on the firing rates of NAc neuronal units in freely behaving rats. On experimental day 1 (ED1), following a saline injection (control), a 30 min baseline neuronal recording was obtained immediately followed by a 2.5 mg/kg i.p. MPD injection and subsequent 60 min neuronal recording. Daily 2.5 mg/kg MPD injections were given on ED2 through ED6 followed by 3 washout days (ED7 to ED9). On ED10, neuronal recordings were resumed from the same animal after a saline and MPD (rechallenge) injection exactly as obtained on ED1. Sixty-seven NAc neuronal units exhibited similar wave shape, form and amplitude on ED1 and ED10 and their firing rates were used for analysis. MPD administration on ED1 elicited firing rate increases and decreases in 54% of NAc units when compared to their baselines. Six consecutive MPD administrations altered the neuronal baseline firing rates of 85% of NAc units. MPD rechallenge on ED10 elicited significant changes in 63% of NAc units. These alterations in firing rates are hypothesized to be through mechanisms that include D1 and D2-like DA receptor induced cellular adaptation and homeostatic adaptations/deregulation caused by acute and chronic MPD administration.
哌醋甲酯（MPD）是一种通过类似于可卡因和安非他命的机制增强中枢神经系统多巴胺能神经传递的精神兴奋剂。负责动物对 MPD 神经元反应的大脑电路的作用机制尚不完全清楚。伏隔核（NAc）已被牵连调节精神兴奋剂的奖励效应。本研究使用永久性植入的微电极来研究 MPD 对自由活动大鼠 NAc 神经元单位放电率的急性和慢性影响。在实验日 1（ED1），在注射盐水（对照）后，立即进行 30 分钟的基线神经元记录，随后进行 2.5 mg/kg 腹腔注射 MPD 并随后进行 60 分钟的神经元记录。在 ED2 至 ED6 期间每天给予 2.5 mg/kg MPD 注射，随后进行 3 天洗脱（ED7 至 ED9）。在 ED10，在相同动物中恢复神经元记录，在盐水和 MPD（再挑战）注射后完全与 ED1 相同。67 个 NAc 神经元单位在 ED1 和 ED10 时表现出相似的波形、形态和幅度，其放电率用于分析。与基线相比，MPD 给药在 ED1 时引起 54%的 NAc 单位放电率增加和减少。连续 6 次 MPD 给药改变了 85%的 NAc 单位的神经元基线放电率。MPD 再挑战在 ED10 时引起 63%的 NAc 单位发生显著变化。这些放电率的改变被假设是通过包括 D1 和 D2 样 DA 受体诱导的细胞适应和急性和慢性 MPD 给药引起的稳态适应/失调的机制。
