Differential responses of circadian Per2 expression rhythms in discrete brain areas to daily injection of methamphetamine and restricted feeding in rats


Correspondence: Dr Ken-ichi Honma, as above.

E-mail: kenhonma@med.hokudai.ac.jp


Behavioral rhythms induced by methamphetamine (MAP) and daily restricted feeding (RF) in rats are independent of the circadian pacemaker in the suprachiasmatic nucleus (SCN), and have been regarded to share a common oscillatory mechanism. In the present study, in order to examine the responses of brain oscillatory systems to MAP and RF, circadian rhythms in clock gene, Period2, expression were measured in several brain areas in rats. Transgenic rats carrying a bioluminescence reporter of Period2-dLuciferase were subjected to either daily injection of MAP or RF of 2 h at a fixed time of day for 14 days. As a result, spontaneous movement and wheel-running activity were greatly enhanced following MAP injection and prior to daily meal under RF. Circadian Per2 rhythms were measured in the cultured brain tissues containing one of the following structures: the olfactory bulb; caudate-putamen; parietal cortex; substantia nigra; and SCN. Except for the SCN, the circadian Per2 rhythms in the brain tissues were significantly phase-delayed by 1.9 h on average in MAP-injected rats as compared with the saline-controls. On the other hand, the circadian rhythms outside the SCN were significantly phase-advanced by 6.3 h on average in rats under RF as compared with those under ad libitum feeding. These findings indicate that the circadian rhythms in specific brain areas of the central dopaminergic system respond differentially to MAP injection and RF, suggesting that different oscillatory mechanisms in the brain underlie the MAP-induced behavior and pre-feeding activity under RF.