Attenuated Response to Stress and Novelty and Hypersensitivity to Seizures in 5-HT4Receptor Knock-Out Mice

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Abstract
To study the functions of 5-HT4receptors, a null mutation was engineered in the corresponding gene. 5-HT4receptor knock-out mice displayed normal feeding and motor behaviors in baseline conditions but abnormal feeding and locomotor behavior in response to stress and novelty. Specifically, stress-induced hypophagia and novelty-induced exploratory activity were attenuated in the knock-out mice. In addition, pentylenetetrazol-induced convulsive responses were enhanced in the knock-out mice, suggesting an increase in neuronal network excitability. These results provide the first example of a genetic deficit that disrupts the ability of stress to reduce feeding and body weight and suggest that 5-HT4receptors may be involved in stress-induced anorexia and seizure susceptibility.