Research reportBlue but not red light stimulation in the dark has antidepressant effect in behavioral despair
Introduction
Light therapy in the form of bright light exposure either early in the morning or in the evening is effective in treating both seasonal [1], [18], [19], [27] and nonseasonal [16], [23] depression. A major target for the antidepressant effect of light administration is the suprachiasmatic nucleus (SCN), the master pacemaker of the brain that regulates a large number of circadian rhythms [45]. The SCN is implicated in affective functions and disorders [10], [20], [21], [39], [40], [44].
Clinical insight gained by light therapy may benefit from animal models that can provide the basis for elucidating the central mechanisms, including the SCN, that mediate the ameliorative effect of light treatment on depression. There is, however, a paucity of studies that have directly tested the effect of light treatment on depression in animals. A study [24] showed that prolonged exposure of male rats to a long photoperiod (14:10 L/D cycle) has an antidepressant effect as measured by reduced immobility in a forced swim test. Conversely, exposure to a short-day regimen has depressogenic effects in rats [30], hamsters [31] and the sand rat [9].
We have been investigating the effect of light administration in the dark phase of a daily L/D cycle on behavioral despair, an animal model of depression. The model is based on two forced swim tests separated by 24 h [29]. Many antidepressants used to treat depression in humans decrease while depressogenic treatments increase immobility in the second swim test compared to the first test [7], [22], [29], [34]. Earlier, we reported that in female Wistar rats a single 12-h exposure to light in the dark phase of a 12:12 L/D lighting cycle provides immunity to behavioral despair [51]. A realistic animal model of light therapy should be able to replicate in animals the clinical findings related to the time of administration of light exposure. In light therapy, morning light exposure has been shown to be more effective than an equivalent treatment in the evening [15], [18], [42], [50]. Light exposure early in the night results in phase delays, whereas light delivered late at night causes phase advances of the SCN [8], [36], [46]. Since morning light treatment is found to be superior to evening light treatment, phase advances rather than phase delays by light exposure may be more effective in antidepressant action of light exposure. In view of these findings, we investigated the potential involvement of the SCN in depression by assessing behavioral despair after brief light exposure at different times in the dark phase of an L/D cycle. We showed recently that a 30-min pulse of light delivered late but not early in the dark phase of a 12:12 L/D cycle has antidepressant effect on female Wistar rats as measured by forced swim tests [38]. The present study expands our previous findings by showing that an even shorter light pulse (10 min) has antidepressant effect in male rats when delivered late but not early in the dark phase of a similar lighting schedule.
Furthermore, since our finding parallels clinical reports on light treatment, we aimed to determine whether the effective late pulse shows spectral sensitivity. With the discovery of intrinsically light sensitive retinal ganglion cells containing melanopsin [32], new insight has been gained on light input to the SCN. Melanopsin-containing ganglion cells provide the major input to the SCN via the retinohypothalamic tract and have maximum spectral sensitivity in the blue region of the visible spectrum [26]. Studies with rodents and humans show that the most effective spectral wavelengths are between 450 and 550 nm for eliciting phase changes and melatonin suppression [12]. A comparison of the antidepressant effects of blue light at 468 nm and red light at 654 nm in humans demonstrated that light at the blue end of the spectrum was much more effective [11]. Our findings indicate that the differential ameliorative effect of late pulses is likely to be due to their different impact on the SCN. Since melanopsin-containing cells in the retina are more sensitive to the wavelengths in the blue rather than the red end of the visible spectrum and constitute the major input to the SCN, it was hypothesized that a brief pulse of blue light delivered in the dark phase of the 12:12 L/D cycle would have a stronger antidepressant effect on behavioral despair than a pulse of red light.
Section snippets
Materials and methods
The study was conducted in two phases in which animals were exposed to a 10-min light pulse (broadband light in Exp.1, blue or red light in Exp.2) late in the dark phase of an L/D cycle followed by forced swim tests.
Experiment 1
Fig. 2A depicts percentages of change in immobility in the second swim test compared to the first test for the groups receiving light treatment at ZT15 or ZT21 and the control group. ANOVA indicated a significant group effect [F (2, 21) = 3.99, p < 0.05] which was due to the significant difference between the group receiving light treatment at ZT21 compared to controls (p < 0.05). The ZT15 group did not differ from control animals.
Experiment 2
Fig. 2B shows the percentage of change in immobility from the first
Discussion
The present study showed that a 10 min pulse of broadband light (1300 lx) has antidepressant effect as measured by immobility in forced swim tests when presented late (at ZT21) but not early (at ZT15) in the dark phase of a 12:12 L/D light cycle. Differential ameliorative effect of broad band light stimulation late but not early in the dark phase of the L/D cycle may have resulted from the fact that photic stimulation at different times in the dark phase of the L/D cycle can affect the
Acknowledgments
We thank Sibel Lacin for her technical assistance in the experiments. This research was supported by grants 07HB701D to RC (Bogazici University Research Fund).
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