Effects of Cannabinoid Receptor Modulation on First Spike Latency in Rat Cerebellar Purkinje Cells Via Whole Cell Recording Under Harmaline Toxicity

Essential tremor (ET) is a neurological disease affecting about 1% worldwide with a considerable impact on quality of life. This condition islinked to the purkinje cells of cerebellum which can be stimulated with harmaline via climbing fibers stemming from inferior olive. Additionally, cannabinoids effects on different parts of CNS including purkinje cells are an advert subject for researchers. As a result, we aimed tofocus on cannabinoid receptors modulation on first spike latency pattern in cerebellar purkinje cells affected by harmaline as an ET simulator. Materials and Methods: Four groups of forty to sixty gram weighted rats were randomly collected; two control groups injected withnormal saline and harmaline each apart, and two other harmaline-injected groups with parallel administration of 1 mg/kg cannabinoid agonist and antagonist, WIN 55,212-2 (WIN) and AM251 respectively. First spike latency response to five levels of positive and negative evoked charges from 0.1 to 0.5 nA was measured by whole cell recording provided by Digidata 1440 and its software (Pclamp 10.1). The data was analyzed by Prism 6. Results: In most positive evoking charges, AM251 significantly propelled the first spike latency pattern to the control group with median of 0.05s delay. This substance did not represent the same results in negative charges remarkably (between 0.04s and 0.2sdelay). While the positive charges in WIN-treated groups resulted in a wide range of delaying times, the negative induced charges brought up some short timeconsuming first spikes. Almost none of WIN patterns demonstrates specific correlation between neither control nor harmaline groups. Conclusion: Considering the observed effects of cannabinoid antagonist on first spike latency pattern of purkinje cells administrated with harmaline, AM251 can be contemplated as a substance reducing the effect of harmaline toxicity which our otherwhole cell recording data can support its role.