Journal zyxwvutsrqponmlkji of zyxwvutsrqponmlk Neurochemistry Raven Press, zyxwvutsrqponm Ltd., New York zyxwvutsrqponm 0 1989 International Society for Neurochemistry Effect of Different Photoperiod Exposure on zy [ 3H]Imipramine Binding and Serotonin Uptake in the Rat Brain Alessandra C. Rovescalli, Nicoletta Brunello, Marco Riva, Roberto Galimberti, and *Giorgio Racagni Center of Neuropharmacology, Institute of Pharmacological Sciences, University of Milan, Milan; and *Institute of Pharmacology, University of Pavia, Pavia, Italy Abstract: Seasonal rhythmicity in the occurrence of acute depressive episodes and the therapeutic efficacy of light ex- posure suggest the possible involvement of the pineal gland or other biological oscillators in the pathophysiology of de- pressive illness. We have performed studies to clarify whether different light/dark (LD) cycle schedules may induce changes in the biochemical targets of antidepressants in the rat CNS. In particular, we have investigated the effect of short- (LD 8: 16) or long-day (LD 14:lO) photoperiods on different bio- chemical parameters of serotonergic neurons. A significant increase in the density of [3H]imipramine(13H]IMI) binding and in the V,,, of 5-[3H]hydroxytryptamine (5-[3H]HT) up- take was found in the hypothalamus of LD 8: 16- with respect to LD 14:10-exposed rats, whereas no difference was found in the kinetic properties of postsynaptic 5-HT receptors and in 5-HT metabolism in the hypothalami and cerebral cortices of rats exposed to the two different photoperiods. A seasonal rhythm of [3H]IMI binding sites and 5-HT uptake seems to exist only in certain brain areas, such as the hypothalamus, because no differences were found in the cerebral cortex of LD 14:lO- and LD 8:16-accustomed rats. [3H]IMI binding and 5-HT uptake were significantly increased in the hypo- thalamus of rats accustomed to a light/dark-inverted cycle (DL 10:14) and killed 6 h after the stopping of lighting in comparison to rats exposed to normal LD 14: 10 cycles and killed 6 h after the beginning of lighting. Therefore, a circadian modification of the serotonergic presynaptic sites seems to be present and related to light/dark exposure. Because the existence of endogenous compounds able to modulate [3H]IMI binding and 5-HT uptake, other than 5-HT, has been postulated in the mammalian brain, the involvement of these substances in the periodic changes observed could be suggested. Key Words: [3H]Imipramine binding-5-Hy- droxytryptamine uptake-Circadian rhythms-Photoperi- ods-Brain-Depression. Rovescalli A. zyx C. zyx et al. Effect of dif- ferent photoperiod exposure on I3H]imiprarninebinding and serotonin uptake in the rat brain. J. Neurochem. 52, 507- 514 (1989). Extensive evidence exists that major depressive dis- orders are characterized by a rhythmic cycle during the year, with the incidence of relapses being clinically higher in the spring and fall. In addition, altered timings of many circadian rhythms in physiological, behavioral, and endocrine functions have been observed in de- pressed patients (Goodwin et al., 1982). Diurnal vari- ations in mood and in the therapeutic efficacy of an- tidepressant drugs have also been observed (Herman, 1984). These findings have led to circadian hypotheses of the pathophysiology of affective disorders, which re- ceived further support from the observation that in- terventions on some biological synchronizers, such as sleep or light exposure, can act as antidepressive ther- Received April 5, 1988; revised manuscript received June 24, 1988; accepted August 2, 1988. Address correspondence and reprint requests to Prof. G. Racagni at Center of Neuropharrnacology, Institute of Pharmacological Sci- ences, Via Balzaretti, 9, 20 I33 Milan, Italy. apies (Pflug and Tolle, 1971; Wehr et al., 1979; Ro- senthal et al., 1986). Early studies in the field of circadian rhythms were devoted to assessing the diurnal pattern of endocri- nological and neurochemical parameters, such as plasma hormonal levels and humoral or tissue con- centrations of neurotransmitters and metabolites (Scheving et al., 1968). More recently, interest has been devoted to the chronobiology of neurotransmitter re- ceptors in the CNS, and the existence of circadian and/ or seasonal rhythms in zyx a- and P-adrenoceptors was demonstrated in the pineal gland and in discrete areas of the brain (Romero et al., 1975; Kaflca et al., 1981). The discovery in the brain of specific recognition Abbreviations used: DL, dark/light; 5-HIAA, 5-hydroxyindoleacetic acid 5-HT, 5-hydroxytryptamine (or serotonin); IMI, imipramine; KET, ketanserin; LD, light/dark; MIA, rnianserin. 507