Decreased behavioral activation following caffeine, amphetamine and darkness in A sub(3) adenosine receptor knock-out mice

• Published in: Physiology & behavior 2008-12, Vol.95 (5), p.668-676
• Main Authors: Bjoerklund, Olga, Halldner-Henriksson, Linda, Yang, Jiangning, Eriksson, Therese M, Jacobson, Marlene A, Dare, Elisabetta, Fredholm, Bertil B
• Format: Article
• Language: English
• ISSN: 0031-9384
• DOI: 10.1016/j.physbeh.2008.09.018

We have examined behavioral consequences of genetic deletion of the adenosine A sub(3) receptors in mice. The open field behavior of A sub(3) adenosine receptor knock-out (A sub(3)R KO) mice was investigated both under basal conditions and after stimulation with psychostimulants. Adolescent (21 day-old) and adult A sub(3)R KO males showed an increase in overall motor activity compared to wild type (WT) males, but the type of activity differed. The motor activity, especially rearing, was also higher in A sub(3)R KO compared to WT adult females. A sub(3) receptors have a low affinity for caffeine and it was therefore surprising to find a decreased response to stimulation with either caffeine or amphetamine in A sub(3)R KO as compared to WT mice in males as well as females. Telemetry recordings also showed a significantly smaller increase in activity upon darkness in A sub(3)R KO. There were no compensatory changes in the mRNA expression of any other adenosine receptor subtypes (A sub(1), A sub(2A) and A sub(2B)) or any changes in dopamine D sub(1) and D sub(2) receptor binding in A sub(3)R KO brains. Challenge with the developmental toxicant methylmercury (1 mu M in drinking water) during pregnancy and lactation did not cause any behavioral alterations in adolescent and adult WT female offspring. In contrast, the A sub(3)R KO female offspring displayed changes in locomotion indicating an interaction between perinatal methylmercury and adenosine A sub(3) receptors. In conclusion, despite low expression of A sub(3) receptors in wild type mouse brain we observed several behavioral consequences of genetic elimination of the adenosine A sub(3) receptors. The possibility that this is due to a role of A sub(3) receptors in development is discussed.