Effects of clomipramine administration on syrian hamster circadian system and behavior

The aim of the present work is to discuss the available data on neonatal an d adult antidepressant treatment in relation to animal models of depression and serotonergic modulation of the circadian system, with a particular emp hasis on our own published and unpublished work on the effects of clomipram ine (a serotonin reuptake inhibitor) on the Syrian hamster circadian behavi or. Neonatal clomipramine treatment (15 mg/kg from postnatal days 8 to 21) significantly augmented the amplitude of the wheel running rhythm, as well as delayed its acrophase and increased the time to reentrain after a 6-h ph ase advance of the light-dark cycle. Neonatally clomipramine-treated hamste rs had a shorter circadian period than saline-treated animals under constan t light - but not under constant dark-conditions, exhibited decreased phase advances after light pulses applied at late subjective night and greater p hase advances after i.p. administration of the 5-HT1A-receptor agonist 8-OH -DPA at midday. These animals also exhibited more locomotor activity than c ontrols, but did not display the typical circadian variation in anxiety-rel ated behavior, as measured in a plus-maze paradigm. They also showed an inc reased 5-HIAA/5-HT ratio in hypothalamus and midbrain raphe, while 5-HT con tent was decreased in frontal cortex and anterior hypothalamic areas. Since drugs linked to the serotonergic system are able to modify the circadian s ystem, we decided to test whether acute and chronic clomipramine administra tion in adulthood was able to change: a) the phase of free running activity rhythms; (b) light-induced phase shifts, and (c) hypothalamic 5-HT turnove r. Acute clomipramine injection had a phase-dependent effect on the free ru nning activity rhythm, with phase advances at CT 0-8 being significantly hi gher than at CT 8-16. Pretreatment with clomipramine inhibited phase advanc es in response to light pulses when applied at CT 19 while phase delays at CT 14 remained unaffected. This acute treatment also decreased 5-HT turnove r in the SCN at both CTs. In contrast, chronic clomipramine administration potentiated light-induced phase advances, without changes in period, amplit ude or central 5-HT turnover. Taken together, these data support the view t hat clomipramine, as other antidepressant drugs, can affect the expression of the circadian rhythmicity in Syrian hamsters, possibly through serotoner gic mechanisms in the case of acute treatments, and more complex behavioral interaction in the case of neonatal and chronic treatments.