Highlights 
● Harmaline caused ultrastructural changes and cell loss in IO and Purkinje cells.
 ● Minocycline reversed passive avoidance learning impairment induced by harmaline.
● Minocycline typically ameliorated harmaline-induced tremors. 
● Minocycline exhibited neuroprotective effects on Purkinje cells and IO neurons.
Plain Language Summary 
Tremor as a rhythmic and sinusoidal movement occurs repeatedly in one or more bodies. It is a common disabling symptom of many motor-related disorders such as Parkinson’s disease, Essential Tremor (ET), Multiple sclerosis, and Huntington disease. Patients with ET have other motor problems which imply cerebellar impairment, such as gait ataxia and eye movement abnormalities as well as non-motor conditions, including cognitive, psychiatric, and sensory abnormalities. According to minocycline ameliorating effect on neurodegenerative diseases, the goal of this study was to assess the possible neuroprotective effects of minocycline on motor and cognitive deficits induced by harmaline in the experimental rat model of ET. The rats were randomly divided into four groups (Saline, Minocycline, Harmaline, and Harmaline + minocycline). Each group went through five different behavioral studies which were performed 30 min after harmaline injection with sequentially 15 min rest intervals among each assay in the following order: tremor score assessment, open field test, footprint, rotarod, wire grip, and passive avoidance task. The results showed that pretreatment with minocycline improved tremor status and memory deficit in the rat’s model of tremor induced by harmaline. The memory impairments observed in harmaline-treated rats were somewhat reversed by administration of minocycline. Minocycline exhibited neuroprotective changes on cerebellar Purkinje cells and inferior olivary neurons. However, minocycline seems to act as a neuroprotective agent to improve tremor severity, gait width disturbance, and memory retrieval impairments induced by harmaline.