NEUROBEHAVIORAL EFFECTS OF ANANDAMIDE AND CANNABINOID RECEPTOR GENE-EXPRESSION IN MICE

The objective of the present study was to determine the neurobehaviora l effects of the putative endogenous cannabinoid ligand, anandamide, a nd its influence on cannabinoid (CB1) receptor gene expression, The ef fect of acute administration of anandamide to C57BL/6, DBA/2, and ICR mice were evaluated in motor function and emotionality tests, The C57B L/6 and ICR mouse strains were more sensitive than the DBA/2 strain to the depression of locomotor activity and stereotyped behavior caused by anandamide. Although anandamide produced catalepsy in all three str ains, anandamide induced ataxia in the minus-maze test only in the C57 BL/6 animals and only at the lowest dose used, In the plus-maze test s ystem, anandamide produced a mild aversive response, and by the third day of treatment the mouse strains developed an intense aversion to th e open arms of the plus-maze, Northern analysis data using the recentl y cloned mouse cannabinoid receptor cDNA as a probe indicated that the re was abundant expression of CB1 gene in the whole brain of the ICR m ouse than in the brains of the C57BL/6 and DBA/2 strains with or witho ut pretreatment with anandamide. The anandamide induced neurobehaviora l profile does not seem to correspond to the CB1 gene expression in th e mouse strains, It is, therefore, unlikely that the CB1 receptor medi ates all the cannabinomimetic effects of anandamide in the brain. (C) 1998 Elsevier Science Inc.