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5‐HT 1B receptor knockout mice show a compensatory reduction in 5‐HT 2C receptor function
Author(s) -
Clifton Peter G.,
Lee Michelle D.,
Somerville Elizabeth. M.,
Kennett Guy A.,
Dourish Colin T.
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02437.x
Subject(s) - knockout mouse , receptor , 5 ht2c receptor , 5 ht receptor , receptor antagonist , biology , endocrinology , medicine , serotonin , agonist , neurotransmitter , antagonist , pharmacology
Although null mutant (‘knockout’) mice have provided valuable animal models to complement traditional approaches to psychopharmacology, such animals may also show complex adaptations to the induced mutation. Here we demonstrate that serotonin 1B (5‐HT 1B ) receptor knockout (KO) mice show adaptations in serotonin 2C (5‐HT 2C ) receptor‐mediated functions. They show smaller reductions in food intake and locomotor activity in response to administration of 5‐HT 2C receptor agonists that are not accounted for by altered drug disposition. These effects are not mimicked by pretreatment of wildtype (WT) mice with a 5‐HT 1B receptor antagonist showing that they result from a longer term adaptation to the loss of 5‐HT 1B receptor function and not from a short‐term interaction between 5‐HT 1B ‐ and 5‐HT 2C ‐mediated functions. In addition, we show that 5‐HT 1B receptor KO mice have a lowered hypothalamic c‐fos response to the administration of 5‐HT 2C receptor agonists. These results demonstrate that compensatory adaptations to the constitutive loss of 5‐HT 1B receptors may be an important determinant of the altered response of 5‐HT 1B KO mice to a variety of pharmacological challenges.