Biopharmaceutics and Biologic Drugs

Essential tremor is one of the most common neurological disorders characterized by uncontrollable shaking and tremors throughout the body. Well known to aff ect adults, it can also aff ect children. Harmaline induced tremor is an established animal model for human essential tremor, but its underlying mechanism and eff ects on mood behavior are still elusive. This study aims to use pharmacological and behavioral methods to investigate the pharmacology in harmaline-induced tremor and the auditory startle response. Mice tremors and auditory startle responses were recorded by the Kinder Startle Monitor System. Harmaline (12.5 mg/kg) reliably induced tremor, and that can be attenuated by ethanol (1.5 mg/kg) and sulpiride (20 mg/kg). In addition, it caused the startle response to decrease signifi cantly. Prepulse inhibition and gap responses also decreased upon harmaline injection and increased the following day, but not signifi cantly from the controls. Supplemental administration following recovery can signifi cantly attenuate gap detection without affecting prepulse inhibition. Our data confi rms the frequency of the tremor was from 10 -15 Hz, and the ethanol eff ect, which indicates validity as novel tremor assay. We also found that harmaline attenuates the auditory startle refl ex by causing the reflex and gap detection to be suppressed, but did not aff ect prepulse inhibition signifi cantly. Th ese fi ndings suggest harmaline not only specifi cally modulates sensory-motor integration, but also the timing of gap detection. Our data provides additional information that D2 receptors are involved in harmaline-induced tremor.