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- Title
The 5-HT [sub1A] receptor in schizophrenia: a promising target for novel atypical neuroleptics?
- Authors
Bantick, R. A.; Deakin, J. F. W.; Grasby, P. M.
- Abstract
Increasing attention is being directed towards the role of the serotonergic system in the neurochemistry of schizophrenia and antipsychotic drug treatment. This review considers the 5-HT 1A receptor in this context. In patients with schizophrenia, the majority of post-mortem studies have reported increases in 5-HT 1A receptor density in the prefrontal cortex in the approximate range 15--80%. Although the pathophysiological significance of this finding is unclear, given the location of a major proportion of these receptors on pyramidal cells, it may reflect an abnormal glutamatergic network. In terms of drug treatment, 5-HT [sub1A] agonists clearly display anticataleptic activity in rats. In addition, 5-HT [sub1A] agonists consistently increase dopamine release in the prefrontal cortex in rodents, which is an effect that might be predicted to improve negative symptoms. 5-HT [sub1A] agonists augment classical neuroleptics in some rat models of antipsychotic action and may be capable of modulating the glutamatergic network therapeutically. Despite the encouraging preclinical data, there is a paucity of clinical studies of 5-HT[sub1A] agonist augmentation of neuroleptics in the treatment of schizophrenia. However, the clinical relevance may be clarified by the atypical antipsychotic drugs clozapine, quetiapine and ziprasidone which combine D 2 receptor antagonism and 5-HT[sub1A] agonism. In conclusion, given the increased prefrontal 5-HT[sub1A] receptor density in the illness, and the anticataleptic activity of 5-HT[sub1A] agonists combined with their ability to evoke prefrontal dopamine release, there is now a sufficient rationale to examine thoroughly the role of the 5-HT[sub1A] receptor in schizophrenia and antipsychotic drug treatment.
- Subjects
SEROTONIN; ANTIPSYCHOTIC agents; SCHIZOPHRENIA treatment; DOPAMINE; PSYCHOPHARMACOLOGY; TESTING
- Publication
Journal of Psychopharmacology, 2001, Vol 15, Issue 1, p37
- ISSN
0269-8811
- Publication type
Article
- DOI
10.1177/026988110101500108