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The 5-HT7 receptor and disorders of the nervous system: an overview Hedlund PBPsychopharmacology (Berl) 2009[Oct]; 206 (3): 345-54RATIONALE: The 5-HT(7) receptor is a more recently discovered G-protein-coupled receptor for serotonin. The functions and possible clinical relevance of this receptor are not yet fully understood. OBJECTIVE: The present paper reviews to what extent the use of animal models of human psychiatric and neurological disorders have implicated the 5-HT(7) receptor in such disorders. The studies have used a combination of pharmacological and genetic tools targeting the receptor to evaluate effects on behavior. RESULTS: Models of anxiety and schizophrenia have yielded mixed results with no clear role for the 5-HT(7) receptor described in these disorders. Some data are available for epilepsy, migraine, and pain but it is still very early to draw any definitive conclusions. There is a considerable amount of evidence supporting a role for the 5-HT(7) receptor in depression. Both blockade and inactivation of the receptor have resulted in an antidepressant-like profile in models of depression. Supporting evidence has also been obtained in sleep studies. Especially interesting are the augmented effects achieved by combining antidepressants and 5-HT(7) receptor antagonists. The antidepressant effect of amisulpride has been shown to most likely be mediated by the 5-HT(7) receptor. CONCLUSIONS: The use of pharmacological and genetic tools in preclinical animal models strongly supports a role for the 5-HT(7) receptor in depression. Indirect evidence exists showing that 5-HT(7) receptor antagonism is clinically useful in the treatment of depression. Available data also indicate a possible involvement of the 5-HT(7) receptor in anxiety, epilepsy, pain, and schizophrenia.|Animals[MESH]|Antidepressive Agents/pharmacology/therapeutic use[MESH]|Disease Models, Animal[MESH]|Humans[MESH]|Nervous System Diseases/drug therapy/genetics/*physiopathology[MESH]|Receptors, Serotonin/drug effects/*metabolism[MESH]|Serotonin Antagonists/pharmacology/*therapeutic use[MESH] |
