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Psychopharmacology (Berl). 1989;97(3):343-8.

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

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Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA 02178.


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 (greater than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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