Cheng Ruey-Kuang, Ali Yusuf M, Meck Warren H
Department of Psychology and Neuroscience, Duke University, 572 Research Drive, Genome Sciences Research Building II, Box 91050, Durham, NC 27708, USA.
Neurobiol Learn Mem. 2007 Sep;88(2):149-59. doi: 10.1016/j.nlm.2007.04.005. Epub 2007 May 21.
The present study examined the clock-speed modulating effects of acute cocaine administration in groups of male rats that received different amounts of baseline training on a 36-s peak-interval procedure prior to initial drug injection. After injection of cocaine (10, 15, or 20mg/kg, ip), rats that had received a minimal amount of training (e.g., <or=30 sessions) prior to drug administration displayed a horizontal leftward shift in their timing functions indicating that the speed of the internal clock was increased. In contrast, rats that had received an extended amount of training (e.g., >or=180 sessions) prior to cocaine (15 mg/kg, ip) administration did not produce this "classic" curve-shift effect, but instead displayed a general disruption of temporal control following drug administration. Importantly, when co-administered with a behaviorally ineffective dose of ketamine (10mg/kg, ip) the ability of cocaine to modulate clock speed in rats receiving extended training was restored. A glutamate "lock/unlock" hypothesis is used to explain the observed dopamine-glutamate interactions as a function of timing behaviors becoming learned habits.
本研究考察了急性给予可卡因对雄性大鼠组时钟速度的调节作用，这些大鼠在首次注射药物前，在36秒峰值间隔程序上接受了不同量的基线训练。注射可卡因（10、15或20mg/kg，腹腔注射）后，在给药前接受最少训练量（如≤30次训练）的大鼠，其计时功能出现水平向左偏移，表明其内部时钟速度加快。相比之下，在给予可卡因（15mg/kg，腹腔注射）前接受大量训练（如≥180次训练）的大鼠，并未产生这种“经典”的曲线偏移效应，而是在给药后出现了时间控制的普遍紊乱。重要的是，当与行为无效剂量的氯胺酮（10mg/kg，腹腔注射）共同给药时，可卡因调节接受大量训练大鼠时钟速度的能力得以恢复。一种谷氨酸“锁定/解锁”假说被用来解释所观察到的多巴胺-谷氨酸相互作用，这种相互作用是随着计时行为成为习得习惯而产生的。
