Shi L H, Luo F, Woodward D J, Chang J Y
Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Winston-Salem, North Carolina 27157, USA.
Synapse. 2005 Jan;55(1):1-16. doi: 10.1002/syn.20088.
The effects of Delta-9-tetrahydrocannabinole (Delta-9-THC) on locomotor activities and related basal ganglia neural responses were investigated in rats. A multiple-channel, single unit recording method was used to record neuronal activity in the dorsal lateral striatum, the globus pallidus, the subthalamic nucleus, and the substantia nigra pars reticulata simultaneously during spontaneous movement and treadmill locomotion. Delta-9-THC treatment (0.05-2.0 mg/kg, i.p.) dose-dependently decreased spontaneous motor activity and altered walking patterns in treadmill locomotion in that stance time was increased and step number was decreased. In parallel with the behavioral effects, Delta-9-THC treatment inhibited neural activity across all four basal ganglia areas recorded during both motor tests. Further, this inhibition of basal ganglia neural activity was behavioral context-dependent. Greater inhibition was found during resting than during walking periods in the treadmill locomotion test. Delta-9-THC treatment also changed firing patterns in the striatum and globus pallidus. More neurons in these regions discharged in an oscillatory pattern during treadmill walking with Delta-9-THC, and the oscillatory frequency was similar to that of the step cycle. Synchronized firing patterns were found in few basal ganglia neurons in the control condition (approximately 1%). Synchronized firing patterns increased during the treadmill resting phase after Delta-9-THC treatment, but still represented a very small proportion of the total neural population (1.9%). The drug treatment did not change neural responses to the tone cue proceeding treadmill locomotion. This study demonstrates dose-dependent inhibitory effects of cannabinoid injection on motor activity. This effect may be related to the behavioral context-dependent inhibition observed in the basal ganglia system where CB1 receptors are densely distributed.
研究了Δ⁹-四氢大麻酚（Δ⁹-THC）对大鼠运动活动及相关基底神经节神经反应的影响。采用多通道单单位记录方法，在大鼠自发运动和跑步机运动期间，同时记录背外侧纹状体、苍白球、丘脑底核和黑质网状部的神经元活动。Δ⁹-THC处理（0.05 - 2.0毫克/千克，腹腔注射）剂量依赖性地降低自发运动活动，并改变跑步机运动中的行走模式，即站立时间增加，步数减少。与行为效应并行，Δ⁹-THC处理在两项运动测试期间均抑制了所记录的所有四个基底神经节区域的神经活动。此外，这种对基底神经节神经活动的抑制依赖于行为背景。在跑步机运动测试中，休息期间比行走期间发现更大的抑制作用。Δ⁹-THC处理还改变了纹状体和苍白球的放电模式。在使用Δ⁹-THC进行跑步机行走期间，这些区域更多的神经元以振荡模式放电，且振荡频率与步周期相似。在对照条件下，很少有基底神经节神经元出现同步放电模式（约1%）。Δ⁹-THC处理后，跑步机休息期同步放电模式增加，但仍占总神经群体的很小比例（1.9%）。药物处理未改变对跑步机运动前音调提示的神经反应。本研究证明了大麻素注射对运动活动的剂量依赖性抑制作用。这种作用可能与在CB1受体密集分布的基底神经节系统中观察到的行为背景依赖性抑制有关。
