Hyponeophagia and arousal in rats: effects of diazepam, 5-methoxy-N,N-dimethyltryptamine, d-amphetamine and food deprivation.

A modified hyponeophagia test in rats serves as an animal model of anxiety. Diazepam at 0.3–3.0 mg/kg acutely reduced hyponeophagia, while 10.0 mg/kg caused sedation and high variability. After seven days of treatment, the dose-response became monotonic and the maximal effect increased, indicating differential tolerance: tolerance develops to the sedative but not the anxiolytic effects. Increased food deprivation did not mimic benzodiazepine effects and actually prolonged eating latency in rats given 5-methoxy-N,N-dimethyltryptamine, arguing against an appetitive interpretation. An arousal hypothesis was supported by d-amphetamine antagonizing the sedative effects of 10.0 mg/kg diazepam. Few sex differences were observed.

Study at a glance

Abstract

A modified hyponeophagia test is described as an animal model of anxiety. The effects of 0, 0.3, 1.0, 3.0 and 10 mg/kg diazepam, given both acutely and for 7 days pretest, were assessed in rats. Acutely, diazepam reduced hyponeophagia over the dose range 0.3-3.0 mg/kg but 10.0 mg/kg produced sedation and large variability. Chronically, the dose-response relationships were monotonic and the maximal effect was increased, suggesting that differential tolerance occurs to the sedative, but not to the anxiolytic, effects of this drug. Increased food deprivation did not mimic benzodiazepine effects on hyponeophagia, and actually prolonged eating latency in rats treated with 5-methoxy-N,N-dimethyltryptamine (2.5 mg/kg), which does not support an interpretation of diazepam effects in terms of appetitive actions. An arousal hypothesis of hyponeophagia was proposed and supported by the antagonism of the sedative effects of 10.0 mg/kg diazepam by d-amphetamine (0.5 mg/kg). Although both male and female rats were used throughout, sex differences were few in these studies.