Attenuated response to stress and novelty and hypersensitivity to seizures in 5-HT4 receptor knock-out mice.
To study the functions of 5-HT4 receptors, a null mutation was engineered in the corresponding gene. 5-HT4 receptor 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-HT4 receptors may be involved in stress-induced anorexia and seizure susceptibility.
Compan
Valérie
V
Unité Propre de Recherche Centre National de la Recherche Scientifique 2580, Génomique fonctionnelle, Montpellier 34094, France. Valerie.Compan@ccipe.cnrs.fr
Zhou
Mingming
M
Grailhe
Régis
R
Gazzara
Russell A
RA
Martin
Renee
R
Gingrich
Jay
J
Dumuis
Aline
A
Brunner
Daniela
D
Bockaert
Joël
J
Hen
René
R
D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D003292:Convulsants; D004435:Eating; D004777:Environment; D018390:Gene Targeting; D008124:Locomotion; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000503:physiopathology; D010433:Pentylenetetrazole; D044422:Receptors, Serotonin, 5-HT4 / Q000235:genetics / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D013312:Stress, Physiological / Q000150:complications*
D003292:Convulsants; D044422:Receptors, Serotonin, 5-HT4; D010433:Pentylenetetrazole