Dept. of Neurobiology and Anatomy, University of Texas Health Science Center at Houston, 6431 Fannin, Houston, TX 77030, USA.
Eur J Pharmacol. 2012 Nov 15;695(1-3):48-56. doi: 10.1016/j.ejphar.2012.08.016. Epub 2012 Sep 18.
The electrophysiological properties of the locus coeruleus (LC) neurons in response to acute and chronic administration of methylphenidate (MPD) were investigated. The extracellular LC neuronal activities were recorded from non-anesthetized, freely behaving rats previously implanted bilaterally with permanent semi microelectrodes. The main findings were: (1) On experimental day 1 (ED1), 87% (94/108) of LC units significantly changed their firing rate after initial (acute) MPD (2.5mg/kg, i.p.) administration. The majority of the responsive units (80%, 75/94) increased their firing rate; (2) Daily MPD (2.5mg/kg) injection was given on ED2 through ED6 followed by 3 washout days (ED7 to 9). On ED10, all LC units exhibited a significant change of their baseline activity compared to their baseline activity on ED1; (3) MPD rechallenge on ED10 elicits 94% (101/108) of LC units significantly changed their firing rate; the majority of them (78%, 79/101) increased their firing rate; (4) The effect of rechallenge MPD administration on ED10 were compared to the effect of initial MPD on ED1, 98% of the LC units exhibited a significant change in their firing rate. 41% (43/106) of them exhibited a significant increase in their firing rate while 59% (63/106) units significantly decreased their firing rate which can be interpreted as electrophysiological sensitization or tolerance respectively. In conclusion, the majority of LC neurons significantly increased their firing rate after acute and chronic MPD administration. This data demonstrated that enhanced LC neuronal activities play important role in the effect of MPD.
研究了急性和慢性哌甲酯（MPD）给药对蓝斑核（LC）神经元电生理特性的影响。通过记录先前双侧植入永久性半微电极的非麻醉、自由活动大鼠的 LC 神经元的细胞外活动来进行实验。主要发现如下：
在实验日 1（ED1），87%（94/108）的 LC 单位在初始（急性）MPD（2.5mg/kg，ip）给药后显著改变其放电率。大多数反应性单位（80%，75/94）增加了放电率；
在 ED2 至 ED6 期间每天给予 MPD（2.5mg/kg）注射，随后进行 3 天的洗脱（ED7 至 9）。在 ED10，与 ED1 时的基线活动相比，所有 LC 单位的基线活动都发生了显著变化；
在 ED10 时重新给予 MPD 挑战会引起 94%（101/108）的 LC 单位显著改变其放电率；其中大多数（78%，79/101）增加了放电率；
将 ED10 时重新给予 MPD 对 LC 单位放电率的影响与 ED1 时给予初始 MPD 的影响进行比较，98%的 LC 单位放电率发生了显著变化。其中 41%（43/106）的单位放电率显著增加，而 59%（63/106）的单位放电率显著降低，这可以分别解释为电生理敏化或耐受。
总之，急性和慢性 MPD 给药后，大多数 LC 神经元的放电率显著增加。这些数据表明，增强的 LC 神经元活动在 MPD 的作用中发挥重要作用。
