Effect of Different Photoperiod Exposure on [³H]Imipramine Binding and Serotonin Uptake in the Rat Brain

Abstract

Seasonal rhythmicity in the occurrence of acute depressive episodes and the therapeutic efficacy of light exposure suggest the possible involvement of the pineal gland or other biological oscillators in the pathophysiology of depressive 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 14:10) photoperiods on different biochemical parameters of serotonergic neurons. A significant increase in the density of [3H]imipramine ([3H]IMI) binding and in the Vmax of 5-[3H]hydroxytryptamine (5-[3H]HT) uptake 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 14:10- and LD 8:16-accustomed rats. [3H]IMI binding and 5-HT uptake were significantly increased in the hypothalamus 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.

Bright-Light Therapy in the Treatment of Mood Disorders

“…Moreover, 5-HTT binding potential values were negatively correlated with the duration of daily sunshine, with reductions in 5-HTT binding parallelling the increase in sunlight during spring. These results are in line with findings on the impact of light on serotonergic processing in rodents [52][53][54][55][56] and they offer a potential explanation for the regular reoccurrence of depressive episodes in patients with SAD and for the spring peak in suicide rates found in temperate and polar zones [57][58][59][60][61] .…”

Seasonal serotonin uptake changes in healthy subjects

“…Interestingly, mesencephalic raphe gives rise to the major 5-HTergic projections, and would seem to be involved in the regulation of endogenous rhythms. The parallel season-related changes in [ 3H]IMI binding and 5-HT uptake, confirmed by another study conducted with animals, although it related an increase in both Bmax and V,nnx values to a decrease in daylight time (Rovescalli et al, 1989), would suggest the presence of a positive correlation between uptake and binding sites. On the other hand, some authors (Costa et al, 1983;Wennogle and Meyerson, 1984) hypothesize an inhibitory activity of the [ 3H]IMI binding sites on the uptake sites.…”

Mechanistic analyses of ion dependences in a high‐affinity human serotonin transport system in transfected murine fibroblast cells

“…When the binding protocol was reversed and [ÅH]imipramine binding level was quantified by using unlabelled 5_HT as competitor, a saturable binding process was again observed and shown to be competitively inhibited by 5_HT. The observed Kd of [ÅH]imipramine binding to intact L_S1 cells compared favourably with Kd values discerned from CNSderived preparations as well as blood platelets (D'Amato et al 1987;Langer & Galzin, 1988;Rovescalli et al 1989), and with imipramine's Ki in inhibiting 5_[ÅH]HT transport by L_S1 cells (Frnka et al 1991). Additionally, binding of both [ÅH]imipramine and 5_ [ÅH]HT to these cells manifested the same Bmax values.…”