Effects of T cycles of light/darkness and periodic forced activity on methamphetamine-induced rhythms in intact and SCN-lesioned rats: explanation by an hourglass-clock model.

In this study intact and suprachiasmatic nuclei (SCN)-lesioned female rats were treated with chronic methamphetamine (MA) via the drinking water. Body temperature, feeding, drinking and wheel-running activity were continuously and automatically recorded. The rats were subjected to light-dark (LD) cycles with period T = 23 hr for 4 months and subsequently T = 25 hr for 3 months. Daily 3-hr forced activity (FA 3:21) was imposed during a few weeks under both LD regimes. MA induced infradian rhythms (period tau s = 28-54 hr) that were found to run parallel in all functions. In intact rats these infradian rhythms showed relative coordination by the LD regime and tau s shortened when T lengthened. In SCN-lesioned rats, however, the infradian rhythms were independent of the LD regime. Under the FA cycles tau s lengthening as well as synchronization was observed. We hypothesized that the MA-induced rhythms reflect a long-period sleep-wake cycle of the hourglass type. We investigated this hypothesis with a modified version of the hourglass-clock model of sleep regulation. Computer simulations showed that this model might offer an explanation for the experimental observations.