Evaluation of Purkinje Neurons and Endocannabinoid Receptors as a Potential Target of Alcoholism Using Japanese Medaka (Oryzias Latipes) as an Animal Model

Purkinje cells (PK) are neurons with large cell bodies found in the central nervous system and are mostly distributed in the cerebellar region of the hindbrain. Several novel markers for PK cells have been developed and are used for characterization of neurobehavioral disorders. The present study was aimed to identify endocannabinoid receptor 1 (CB1) as a potential marker of PK cells and evaluate them as a molecular target of alcohol and cerebellar functions using Japanese medaka (Oryzias latipes) as an animal model. Previously, we have observed that medaka genome consist three CB receptor paralogs; two of them (cnr1a and cnr1b) showed structural identity with human. We have also observed that expression of cnr1a mRNA in medaka embryos was disrupted by developmental ethanol exposure. Moreover, exposure to waterborne ethanol (300mM) is able to alter the swimming behavior of the adult male medaka within 1 hour of exposure. Preliminary data indicate that the CB1 receptor protein is expressed in the dendritic region and axon terminals of PK cells. It also indicates that the morphology of the PK cells and the density of CB1 receptors was altered due to alcohol exposure. We expect that these alterations are mediated by disruption of the expression of cnr1a receptor (CB1) in the brain.