Abstract
A common feature of mood disorders is disturbances of circadian rhythm and fluctuations in body weight. These are also common side effects of clinical anxiolytics. Likewise, those with eating disorders usually have comorbid anxiety disorders. This suggests that there may be some link between eating, mood, and circadian rhythmicity. The hippocampus is involved in the control of anxiety; and circadian periodicity in the firing rates of pyramidal cells in area CA1 of the hippocampus has been linked to a food-entrainable oscillator. As this evidence links the hippocampus to anxiety, food, and circadian rhythmicity, this thesis examined whether reticular-elicited hippocampal RSA, a reliable assay of anxiolytic action, is modulated diurnally and/or by food. The effects of food on mood could be due to leptin – a hormone secreted in response to fat ingestion, which also shows a diurnal cycle. Leptin has been shown to be an effective anxiolytic in some behavioural tests of anxiety, but not others. So, this thesis also examined the effect of leptin on two test of anxiolytic potential linked to hippocampal function. Leptin was tested both on reticular-elicited hippocampal RSA and on an FI60 task. Both of these tests are reliable indicators of anxiolytic potential. We predicted that our hippocampal RSA test of anxiety would show a food-modulated circadian pattern of oscillation; and that leptin would have an anxiolytic-like effect on both reticular-stimulated hippocampal RSA and behaviour in the FI60. Six rats were implanted with bipolar hippocampal recording electrodes and bipolar reticular stimulating electrodes. RSA was elicited every hour for either 48 hours (food as normal at 1800hours) or 58 hours (food 2, 26 and 50 hours after recording started). Starting times were staggered throughout the day. Circadian oscillation of hippocampal RSA was unclear, however unexpected feeding decreased overall RSA frequency in an anxiolytic manner. Two animals were then administered leptin at doses 0mg/kg (control), 0.5mg/kg, and 1mg/kg (i.p.) and produced a 30 – 90 minute dose-dependent increase in the slope of the stimulation/frequency function of but did not change overall frequency. In the FI60 task 0.5mg/kg of leptin produced an anxiolytic-like effect similar to that shown by the active control chlordiazepoxide and the 1.0mg/kg dose produced an overall depression in responding similar to buspirone and fluoxetine. These results are largely consistent with previous effects of serotonergic anxiolytics and suggest that leptin may have some serotonergic anxiolytic action coupled with serotonergic release of corticosterone.