Peter B Hedlund1. 1. Department of Molecular Biology, MB10, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. hedlund@scripps.edu
Abstract
RATIONALE: 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.
RATIONALE: 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 humanpsychiatric 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.
Authors: Therese M Eriksson; Armita Golkar; Joanna C Ekström; Per Svenningsson; Sven Ove Ogren Journal: Eur J Pharmacol Date: 2008-08-29 Impact factor: 4.432
Authors: Alex Brenchat; Luz Romero; Mónica García; Marta Pujol; Javier Burgueño; Antoni Torrens; Michel Hamon; José Manuel Baeyens; Helmut Buschmann; Daniel Zamanillo; José Miguel Vela Journal: Pain Date: 2008-12-31 Impact factor: 6.961