Depletion of brain serotonin by 5,7-DHT modifies hamster circadian rhythm response to light

Abstract

The midbrain raphe complex innervates the circadian rhythm regulating system by direct projections to the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL). The present experiments examined the changes in circadian rhythm regulation consequent to the depletion of brain serotonin by central 5,7-dihydroxytryptamine (DHT) application. Adult male hamsters with access to running wheels were entrained to a light-dark cycle 14:10 (LD) of photoperiod, pre-treated with desmethylimipramine and given bilateral lateral ventricle infusions of 75 micrograms DHT/2.5 microliters 0.5% ascorbic acid in saline or vehicle only. Two separate experiments were performed. Four weeks after surgery, animals were transferred to either constant light (LL; Experiment 1) or constant dark (DD; Experiment 2). Animals remained in LL for 85 days, then were transferred to DD for 50 days, followed by a return to LD 14:10 for 14 days. Animals in Expt. 2 remained in DD for 55 days, were given 3 days food deprivation, then, beginning 35 days later, were periodically exposed to 30 min light pulses as a phase response curve (PRC) to light was generated. DHT treatment induced rapid appearance of advanced activity onset, delayed offset and longer duration of the nocturnal activity phase. DHT animals in LL had circadian locomotor rhythms much longer than control animals (24.43 +/- 0.04 vs 24.19 +/- 0.05 h) and normal circadian rhythmicity was rapidly lost by DHT animals in LL. There was no effect of DHT on circadian period in DD, but the DHT treated animals in DD had a larger phase delay region of the PRC than did controls and this was associated with an overall change in the temporal properties of the PRC. Serotonin immunohistochemistry showed an approximate 90% loss of cells from the dorsal raphe nucleus and decreased density of the serotonergic terminal field in the SCN and IGL. The results support the view that the serotonergic system modulates the phasic actions of light on the hamster circadian rhythm system. The data also indicate that hamsters can have a Type 0 PRC.