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.
Interactions between 5-MeODMT, chlordiazepoxide, and pCPA on conflict behavior were examined. 5-MeODMT at 1.0 and 3.0 mg/kg reduced unpunished response rates but did not affect punished behavior alone or with chlordiazepoxide. However, 5-MeODMT at 1 mg/kg reversed the anti-conflict effects of chronic pCPA (100 mg/kg). Chronic pCPA did not prevent increased punished responses from chlordiazepoxide (5 mg/kg). These findings suggest benzodiazepines act at a site distal to serotonergic drugs on conflict behavior.
Serotonin agonists fenfluramine and 5-MeODMT increased hyponeophagia (suppression of feeding in a novel environment) in rats, while diazepam reduced it and counteracted the effects of both serotonin agonists. Diazepam appears to act downstream of serotonergic drugs in modulating this behavior.
In rats selectively bred for avoidance learning, the drug 5-MeODMT (2.5 mg/kg) reduced feeding in a novel environment, while diazepam (1 mg/kg), methysergide, and 1-propranolol (6 mg/kg) increased it; d-propranolol had no effect. Roman Low Avoidance rats were most sensitive to all drugs and showed the strongest neophobia. Female Roman High and Control Avoidance rats were more sensitive to 5-MeODMT than males. These strain and sex differences suggest links between arousal, biochemical traits, and drug responsiveness.