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126 MICE OVEREXPRESSING THE 5-HTIA RECEPTOR IN CORTEX AND DENTATE GYRUS
B. Bert, N. Wilhelmi, P. Gerhards, H. Kusserow, F. Theuring, H. Final
linstitute for Pharmacology and Toxicology, Faculty of Veterinary Medicine, Freie Universität Berlin, 14195 Berlin and Institute for Pharmacology and Toxicology, Charité - Medical School Berlin, Humboldt-Universität, 10098 Berlin
The serotonin 1A (5-HT1A) receptor is one of the best described receptor subtypes of the serotonergic system. However, the complex distribution pattern, the pre- and postsynaptic localisation, the impact on 5-HT, noradrenaline and acetylcholine release, as well as the influence on a wide range of physiological functions aggravate the attribution of 5-HTIA agonist effects to the behavioural outcomes. For the investigation of the postsynaptic receptor subtype a mouse line with a high overexpression of the 5-HT1A receptor in the outer laminae of the cortex and in the dentate gyrus were used. A first survey revealed no differences in locomotor activity and anxiety-related behaviour between transgenic and wildtype mice. Merely the body temperature of male transgenic mice was lower than of the control group. To clarify whether stimulation of the overexpressed receptors leads to differing responses, the animals received the 5-HT1A agonist 8-OH-DPAT in a dosage from 0.1 to 2.0 mg/kg i.p., and anxiety-related behaviour and motor activity were tested. Furthermore, the occurrence of the 5-HT syndrome and changes in body temperature were investigated. 8-OH-DPAT did not affect anxietyrelated behaviour either in transgenic or control mice. However, motor activity as weil as body temperature of transgenic mice was more influenced by 8-OH-DPAT compared to wildtype mice: one third of transgenic mice were totally inactive after receiving a lower dose of 8-OH-DPAT (0.5 mg/kg), and unexpected behaviours like ,backward walking' and 'head waving' appeared. In contrast, motor activity of wildtype mice was only reduced by higher dose (1.0 mg/kg) 8-OH-DPAT and 1.5 mg/kg were able to provoke the 5-HT syndrome. Moreover, body temperature of transgenic mice extremely declined (>3°C) after the injection of 0.5 mg/kg 8-OH-DPAT, whereas in control mice the body temperature only dropped down 1°C. Therefore, we conclude that the overexpressed and postsynaptically distributed 5-HT1A receptors are also pharmacological active. These mice seem to be a promising model to further investigate postsynaptic regulated functions as the 5-HT syndrome and regulation of the body temperature. They also can serve as a model for screening 5-HTIA agonists and antagonists. Investigations were supported by DFG grant FI 491/2-3.