Dual regulation of clock gene Per2 expression in discrete brain areas by the circadian pacemaker and methamphetamine-induced oscillator in rats

• Published in: The European journal of neuroscience 2014-01, Vol.39 (2), p.229-240
• Main Authors: Natsubori, Akiyo, Honma, Ken-ichi, Honma, Sato
• Format: Article
• Language: English
• Subjects: Animals; behavioral rhythm; Biological and medical sciences; Brain - drug effects; Brain - physiology; brain dopaminergic system; Chronobiology; Circadian Clocks - drug effects; Circadian Rhythm - drug effects; Dopamine Agents - pharmacology; Drinking - drug effects; Drinking - physiology; Eating - drug effects; Eating - physiology; extra-SCN oscillator; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; In Vitro Techniques; Locomotion - drug effects; Locomotion - physiology; luciferase reporter; Medical sciences; Methamphetamine - pharmacology; Neuropharmacology; Period Circadian Proteins - metabolism; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Suprachiasmatic Nucleus - drug effects; Suprachiasmatic Nucleus - physiology; Time Factors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Wakefulness - drug effects; Wakefulness - physiology
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.12400

Behavioral rhythms induced by methamphetamine (MAP) treatment in rats are independent of the circadian pacemaker in the suprachiasmatic nucleus (SCN). To know the site and mechanism of an underlying oscillation (MAP‐induced oscillator; MAO), extra‐SCN circadian rhythms in the discrete brain areas were examined in rats with and without the SCN. To fix the phase of MAO, MAP was supplied in drinking water at a restricted time of day for 14 days (R‐MAP) and subsequently given ad libitum (ad‐MAP). Plain water was given to the controls at the same restricted time (R‐Water). Clock gene Per2 expression was measured by a bioluminescence reporter in cultured brain tissues. In SCN‐intact rats, MAO was induced by R‐MAP and behavioral rhythms were phase‐delayed from the restricted time under ad‐MAP with relative coordination. Circadian Per2 rhythms in R‐MAP rats were not affected in the SCN but were slightly phase‐advanced in the olfactory bulb (OB), caudate–putamen (CPU) and substantia nigra (SN) as compared with R‐Water rats. Following SCN lesion, R‐MAP‐induced MAO phase‐shifted more slowly and did not show a sign of relative coordination. In these rats, circadian Per2 rhythms were significantly phase‐shifted in the OB and SN as compared with SCN‐intact rats. These findings indicate that MAO was induced by MAP given at a restricted time of day in association with phase‐shifts of the extra‐SCN circadian oscillators in the brain dopaminergic areas. The findings also suggest that these extra‐SCN oscillators are the components of MAO and receive dual regulation by MAO and the SCN circadian pacemaker. Periodic administration of methamphetamine containing water to rats induced an oscillation (MAO) independent of the circadian pacemaker in the suprachiasmatic nucleus (SCN). Bilateral SCN lesions accelerated MAO‐induced changes of the circadian Per2 expression rhythms in several areas of brain dopaminergic system, indicating that MAO and SCN pacemaker regulate coordinately the extra‐SCN circadian oscillators in these areas. Differential coordination suggests that they are the components of MAO.