The effect of memantine in harmaline-induced tremor and neurodegeneration
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2011Author
İşeri, Pervin K.Karson, Ayşe
Güllü, Kemal M.
Akman, Özlem
Köktürk, Sibel
Yardımoğlu, Melda
Ateş, Nurbay
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Iseri PK, Karson A, Gullu KM, Akman O, Kokturk S, Yardimoglu M, Erturk S, Ates N. The effect of memantine in harmaline-induced tremor and neurodegeneration. Neuropharmacology. 2011; 61(4): 715-723. doi: 10.1016/j.neuropharm.2011.05.015.Abstract
Essential tremor (ET) is one of the most common and most disabling movement disorders among adults.
The drug treatment of ET remains unsatisfactory. Additional therapies are required for patients with
inadequate response or intolerable side effects. The current study aims to investigate the anti-tremogenic
and neuroprotective effects of memantine (NMDA receptor antagonist) on the harmaline model of transient
action tremor. The effects of memantine were further compared with ethanol. Three separate groups
of male Wistar rats were injected either with saline, ethanol (1.5 gr/kg), or memantine (5 mg/kg) 15 min
prior to a single intraperitoneal injection of harmaline (20 mg/kg). Tremor and locomotion were evaluated
by a custom-built tremor and locomotion analysis system. After 24 h of harmaline injection, cellular
viability, and apoptosis were assessed using crystal violet staining, and caspase-3 immunostaining,
respectively. Harmaline caused neuronal cell loss and caspase-3 mediated apoptosis in cerebellar granular
and purkinje cells as well as the inferior olivary neurons. Despite a reduction in tremor intensity and
duration with ethanol, this compound resulted in cell loss in cerebellum and olivary nucleus. Memantine
exhibited neuroprotective efficacy on cerebellar and inferior olivary neurons albeit weaker anti-tremor
effect compared to ethanol. In conclusion, anti-tremogenic and neuroprotective effects do not necessarily
overlap. Memantine is a potential treatment for ET particularly given its neuroprotective efficacy.