Effects of selective monoaminergic reuptake blockade on activity rhythms in developing rats

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Abstract
Developing rats display prominent ultradian rhythms of locomotor activity when separated from the litter. A pharmacological analysis was undertaken to provide preliminary data on the role of monoaminergic neurotransmitter systems in the modulation or manifestation of this fundamental biological rhythm. Twenty-four hour activity profiles were monitored in 15-day-old rats, tested in darkness, after intraperitoneal treatment with desipramine (DMI), zimelidine (ZMI), or GBR-13069 (GBR), selective uptake inhibitors of norepinephrine, serotonin, and dopamine, respectively. Time series data were analyzed by low-resolution variance spectral analysis. DMI significantly diminished ultradian (>1 cycle per day; cpd) rhythmicity, and enhanced the circadian rhythm. Equimolar doses of ZMI had little effect on the ultradian band (7–15 cpd), but slightly reduced the circadian peak. The effects of acute GBR administration were complex, as this agent produced prominent effects on basal activity. In a second study these agents were administered continuously over a 5-day period, using subcutaneously implanted Alzet osmotic minipumps, to avoid the confounding effects of acute administration. Continuously-infused DMI virtually eliminated characteristic ultradian rhythms in the 9–15 cpd bandwidth. ZIM diminished ultradian oscillations only in the 14–15 cpd range, and GBR-12909 had little effect on ultradian rhythms throughout the usually prominent 7–16 cpd domain. All three reuptake inhibitors increased the prominence of slow ultradian rhythms with frequencies of 3–4 cpd. Continuous reuptake blockade had no significant effects on circadian amplitude or phase, as determined by cosinor analysis. Overall, these results indicate that modulation of activity rhythms in the neonatal rat are prominently affected by drugs which enhance certain central monoaminergic systems, particularly norepinephrine.