DIURNAL-VARIATIONS OF SEROTONIN AND DOPAMINE LEVELS IN DISCRETE BRAIN-REGIONS OF SYRIAN-HAMSTERS AND THEIR MODIFICATION BY CHRONIC CLORGYLINE TREATMENT

In Syrian hamsters, chronic administration of the type A monoamine oxidase inhibitor, clorgyline (CLG), alters the intrinsic period and daily pattern of the circadian rhythm of wheel running, and changes the intensity-response curve for phase-shifting of the rhythm by light pulses. Chronic treatment with CLG also decreases hypothalamic and peritoneal temperatures, particularly during the rest phase of the activity-rest cycle. To help identify monoamines that may mediate CLG's effects on circadian rhythms, we measured levels of dopamine (DA) and serotonin (5-HT) at nine time points over a 24-h period in micro-dissected brain regions in chronic CLG-treated or saline-treated hamsters. For 5-HT, a diurnal variation was detected in all regions in saline-treated animals; for DA, no diurnal variation was detected in any region. In all regions. 5-HT levels and, to a lesser extent, DA levels were higher after CLG treatment. The acrophase of the 5-HT rhythm in the suprachiasmatic nucleus (SCN) was delayed by CLG-treatment, while the acrophase in the dorsal raphe nucleus was unchanged. The diurnal variation of 5-HT in the paraventricular nucleus of the hypothalamus, medial preoptic area, and median raphe nuclei was no longer detectable after chronic CLG-treatment. The phase-delay induced by CLG treatment in the daily rhythm of serotonin levels in the SCN, which functions as a circadian pacemaker, may be an important mechanism underlying the drug's capacity to slow the intrinsic rhythm of the pacemaker and to phase-delay behavioral rhythms that are under its control.