MONOAMINE DEPLETION ALTERS THE ENTRAINMENT AND THE RESPONSE TO LIGHT OF THE CIRCADIAN ACTIVITY RHYTHM IN HAMSTERS

Reduced amplitude, shorter free-running periods and desynchronization among a number of circadian rhythms are associated with advanced age in rodents. The response of the hamster circadian system to photic stimuli is also altered during senescence. Decreased monoamine levels, receptor sites and neuronal populations are commonly observed in the aging brain. The objective of the present study was to determine if monoamine depletion with reserpine in young hamsters induces changes in the circadian rhythm of locomotor activity similar to those that occur spontaneously with aging. Wheel-running activity of 12 young hamsters under a 14 h-light/10 h-dark cycle was continuously monitored. The total activity level, the times of activity onset, peak and offset and the duration of activity were determined during a 1-week period after vehicle treatment and for three 1-week periods after reserpine treatment (4 mg/kg). A second group of eight reserpine-treated and six vehicle-treated animals was kept in constant darkness (DD). The period of the circadian activity rhythm in DD and the phase-shifts after short light pulses at circadian time 19 (CT19) were determined in the control and reserpine-treated groups. Brain monoamines in the hypothalamus, striatum and pons/medulla after reserpine and vehicle treatment were determined by high-pressure liquid chromatography. The data were analyzed with chi2 periodogram and one-way ANOVA followed by Duncan's post hoc test. Reserpine treatment significantly reduced total wheel-running activity and the monoamine levels in the hypothalamus, striatum and pons/medulla. The onset and peak of entrained activity after reserpine occurred earlier relative to the light/dark (LD) cycle; the offset of activity was delayed and the duration of the activity phase was prolonged. The circadian rhythm of locomotor activity in DD after reserpine treatment persisted with reduced amplitude and longer free-running period and the phase advances in response to light pulses at CT19 were dramatically augmented. The pattern of changes in the circadian rhythm of locomotor activity after reserpine treatment resembles that observed in old animals. Our results raise the possibility that the age-related alterations in the circadian system might be associated with deficits in the monoaminergic neurotransmission.