Date of Award


Level of Access Assigned by Author

Open-Access Dissertation

Degree Name

Doctor of Philosophy (PhD)




Alan M. Rosenwasser

Second Committee Member

Ziad Boulos

Third Committee Member

Michael Robbins


Neonatal exposure to monoaminergic antidepressant drugs produces a wide variety of effects on the behavior and physiology of adult rats which parallel those observed in human depression. Monoaminergic neurotransmitter systems are involved in the regulation of both affective and circadian behaviors, and alterations in circadian rhythmicity have been observed in depressed patients and in several other animal depression models. The purpose of the present study was to explore circadian phase shifting following neonatal antidepressant treatment. Neonatal rats were divided into three treatment groups; a clomipramine-treated group, a saline-treated group, and an unhandled group. Daily injections of clomipramine (25 mg/kg SC), a serotonin (5-HT) re uptake inhibitor, or saline were given from postnatal day 8-21. The saline-treated group served as a control for the pharmacological effects of clomipramine, while the unhandled group was included to control for any stressors associated with the injection procedure. As adults, rats participated in one of two separate experiments designed to assess non-photic and photic phase shifting. In the non-photic experiment, stimuli included injections of 8-OH-DPAT (5mgIkg ip), a 5-HT agonist, and six-hour dark pulses, both of which were presented during subjective day. A significant difference was found between the clomipramine and saline-treated groups in both the size and direction of 8-OH-DPAT-induced phase shifts, as the clomipramine-treated group displayed a small phase advance while the saline-treated group showed a larger phase delay. Following dark pulses, all groups displayed mean phase advances, but no significant group differences were observed. For both 8-OH-DPAT and dark pulses however, the pattern of responses across the three neonatal groups indicates that neonatal clomipramine and saline treatment may have opposite effects on non-photic phase shifting. In the photic experiment, rats were presented with light pulses during early and late subjective night, but no significant group differences were found in the magnitude of the resulting phase shifts. Taken together, results of this study suggest that neonatal clomipramine treatment alters non-photic, but not photic phase shifting, and comparisons of the present results with those reported previously, provide support for species differences in the role of serotonin in circadian regulation.