| 1 | Neuropsychopharmacology 2015 Nov 40: 2764-73 |
|---|---|
| PMID | 25936642 |
| Title | Mice Lacking the Serotonin Htr2B Receptor Gene Present an Antipsychotic-Sensitive Schizophrenic-Like Phenotype. |
| Abstract | Impulsivity and hyperactivity share common ground with numerous mental disorders, includingschizophrenia. Recently, a population-specific serotonin 2B (5-HT2B) receptor stop codon (ie,HTR2BQ20*) was reported to segregate with severely impulsive individuals, whereas 5-HT2B mutant (HTR2B(-/-)) mice also showed high impulsivity. Interestingly, in the same cohort, early-onsetschizophreniawas more prevalent inHTR2BQ*20 carriers. However, the putative role of 5-HT2B receptor in the neurobiology ofschizophreniahas never been investigated. We assessed the effects of the genetic and the pharmacological ablation of 5-HT2B receptors in mice subjected to a comprehensive series of behavioral test screenings for精神分裂症-like symptoms and investigated relevant dopaminergic and glutamatergic neurochemical alterations in the cortex and the striatum. Domains related to the positive, negative, and cognitive symptom clusters ofschizophreniawere affected inHTR2B(-/-) mice, as shown by deficits in sensorimotor gating, in selective attention, in social interactions, and in learning and memory processes. In addition,HTR2B(-/-) mice presented with enhanced locomotor response to the psychostimulants dizocilpine and amphetamine, and with robust alterations in sleep architecture. Moreover, ablation of 5-HT2B receptors induced a region-selective decrease of dopamine and glutamate concentrations in the dorsal striatum. Importantly, selected精神分裂症-like phenotypes and endophenotypes were rescued by chronic haloperidol treatment. We report herein that 5-HT2B receptor deficiency confers a wide spectrum of antipsychotic-sensitive精神分裂症-like behavioral and psychopharmacological phenotypes in mice and provide first evidence for a role of 5-HT2B receptors in the neurobiology of psychotic disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Neuropsychopharmacology 2015 Nov 40: 2764-73 |
| PMID | 25936642 |
| Title | Mice Lacking the Serotonin Htr2B Receptor Gene Present an Antipsychotic-Sensitive Schizophrenic-Like Phenotype. |
| Abstract | Impulsivity and hyperactivity share common ground with numerous mental disorders, includingschizophrenia. Recently, a population-specific serotonin 2B (5-HT2B) receptor stop codon (ie,HTR2BQ20*) was reported to segregate with severely impulsive individuals, whereas 5-HT2B mutant (HTR2B(-/-)) mice also showed high impulsivity. Interestingly, in the same cohort, early-onsetschizophreniawas more prevalent inHTR2BQ*20 carriers. However, the putative role of 5-HT2B receptor in the neurobiology ofschizophreniahas never been investigated. We assessed the effects of the genetic and the pharmacological ablation of 5-HT2B receptors in mice subjected to a comprehensive series of behavioral test screenings for精神分裂症-like symptoms and investigated relevant dopaminergic and glutamatergic neurochemical alterations in the cortex and the striatum. Domains related to the positive, negative, and cognitive symptom clusters ofschizophreniawere affected inHTR2B(-/-) mice, as shown by deficits in sensorimotor gating, in selective attention, in social interactions, and in learning and memory processes. In addition,HTR2B(-/-) mice presented with enhanced locomotor response to the psychostimulants dizocilpine and amphetamine, and with robust alterations in sleep architecture. Moreover, ablation of 5-HT2B receptors induced a region-selective decrease of dopamine and glutamate concentrations in the dorsal striatum. Importantly, selected精神分裂症-like phenotypes and endophenotypes were rescued by chronic haloperidol treatment. We report herein that 5-HT2B receptor deficiency confers a wide spectrum of antipsychotic-sensitive精神分裂症-like behavioral and psychopharmacological phenotypes in mice and provide first evidence for a role of 5-HT2B receptors in the neurobiology of psychotic disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |