Mice Over-expressing the 5-ht(1a) Receptor in Cortex and Dentate Gyrus Display Exaggerated Locomotor and Hypothermic Response to 8-oh-dpat.
From: Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Koserstrasse 20, 14195 Berlin, Germany. bert.bettina@vetmed.fu-berlin.de
Behavioural brain research
- Publish Date: Feb 2006
- ISSN: 0166-4328
- Volume: 167
- Issue: 2
- Pages: 328-41
- Medium: Print
- Language: English
- Citation (JAMA): Bert Bettina, Fink Heidrun, Hörtnagl Heide, et al. Mice Over-expressing the 5-ht(1a) Receptor in Cortex and Dentate Gyrus Display Exaggerated Locomotor and Hypothermic Response to 8-oh-dpat.. Behav. Brain Res. Feb 2006;167:328-41
Abstract
The serotonin 1A (5-HT(1A)) receptor is one of the best described receptor subtypes of the serotonergic system. Due to the complex distribution pattern, the pre- and postsynaptic localisation, the impact on various monoamines, as well as the influence on a wide range of physiological functions, the contribution of 5-HT(1A) receptors to behavioural outcomes is difficult to define. In this study, we present a new transgenic mouse model with a prominent over-expression of the 5-HT(1A) receptor in the outer cortical layers (I-III) and the dentate gyrus. Behavioural studies revealed a slight decrease in baseline motor activity of homozygous mice during the open field test. Moreover, core body temperature of male transgenic mice was significantly lower than that of wild-type mice. Pharmacological studies with the 5-HT(1A) receptor agonist 8-OH-DPAT (0.1-2.5 mg/kg, i.p.) revealed an exaggerated drug response in mutant mice. 8-OH-DPAT led to a drastic decrease in motor activity in the open field and elevated plus maze test. This significant effect on motor activity became more apparent by investigating the serotonergic syndrome induced by 8-OH-DPAT. Concentration as low as 0.5 mg/kg 8-OH-DPAT caused immobility in transgenic mice for 30 min, head weaving behaviour, and backward walking, whereas in wild-type animals, typical behaviours of the serotonin syndrome were first observed at concentrations of 1.5 mg/kg and more. In addition, the 8-OH-DPAT induced hypothermia was more pronounced in mutant mice than in wild-type animals. Therefore, these genetically modified mice represent a promising model for further investigations of the role of 5-HT(1A) receptors.
Mesh Headings (Keywords): 8-Hydroxy-2-(di-n-propylamino)tetralin, Animals, Cerebral Cortex, Dentate Gyrus, Dose-Response Relationship, Drug, Exploratory Behavior, Female, Hypothermia, Immobility Response, Tonic, Male, Mice, Mice, Transgenic, Motor Activity, Receptor, Serotonin, 5-HT1A, Serotonin Agonists, Serotonin Syndrome
Check for Full Text / PubMed Unique Identifier (PMID): 16256213
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