Effects of antidepressants on entrainment of circadian rhythms

1. Anti-depressant drugs alter the period of circadian rhythms under free running conditions. We have examined whether treatment with anti-depressants alters such rhythms under conditions of entrainment to a lighting cycle or following a phase advance of the lighting. 2. In the first experiment, following entrainment to a 10L:14D lighting schedule, male Long Evans rats were injected daily for three weeks, with either saline, desipramine or clomipramine at a dose of 10 mg/kg. Under these conditions, the resting circadian patterns of serum corticosterone and melatonin were not affected. 3. In a second experiment, male Wistar rats, adapted to a 12L:12D lighting cycle, were implanted with transmitters, permitting continuous recording of temperature. Animals were given chow supplemented with clomipramine or desipramine so that plasma clomipramine levels were within the normal therapeutic range for humans and desipramine levels were at 4-6 times the therapeutic range. After three weeks of drug treatment, the mean 24 h pattern of temperature was decreased and phase advanced by 72 min in the desipramine group compared to clomipramine or controls. Following a 6 h phase advance in the lighting cycle, the three groups responded differently. The clomipramine group evidenced the most rapid advance in the acrophase, equivalent to 6.9 h, while the saline and desipramine treated groups re-entrained significantly more slowly. 4. Clomipramine, given to achieve clinically meaningful blood levels, does not alter the circadian temperature rhythm under constant conditions of alternating light and dark, but significantly accelerates the rate of re-entrainment to a 6 h phase advance of the lighting schedule.