Peripubertal mGluR2/3 Agonist Treatment Prevents Hippocampal Dysfunction and Dopamine System Hyperactivity in Adulthood in MAM Model of Schizophrenia
| Autor: | Susan F. Sonnenschein, Anthony A. Grace |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Agonist
Male medicine.medical_specialty Methylazoxymethanol Acetate medicine.drug_class Population Neurotoxins Hippocampus Hippocampal formation Receptors Metabotropic Glutamate 03 medical and health sciences 0302 clinical medicine Dopamine Internal medicine medicine Excitatory Amino Acid Agonists Animals Amino Acids education education.field_of_study Behavior Animal business.industry Ventral Tegmental Area Glutamate receptor Age Factors 030227 psychiatry Rats Psychiatry and Mental health Disease Models Animal medicine.anatomical_structure Endocrinology Metabotropic glutamate receptor Schizophrenia Neuron business 030217 neurology & neurosurgery medicine.drug Antipsychotic Agents Regular Articles |
| Zdroj: | Schizophr Bull |
| ISSN: | 1745-1701 |
| Popis: | Pomaglumetad methionil (POM), a group 2 metabotropic glutamate receptor (mGluR2/3) agonist, showed promise as a novel antipsychotic in preclinical research but failed to show efficacy in clinical trials, though it has been suggested that it may be effective in certain patient populations, including early in disease patients. We used the methyazoxymethanol acetate (MAM) rat model of schizophrenia to determine whether POM may prevent the development of dopamine (DA) system dysfunction in a model representative of the hyperdopaminergic state thought to underlie psychosis, compared to control (SAL) rats. MAM and SAL rats were administered either POM (3 mg/kg, i.p.), vehicle (1 ml/kg), or no injection during postnatal day (PD) 31–40. In either late adolescence (PD 47–56) or adulthood (PD 83–96), novel object recognition (NOR) was tested, followed by anesthetized in vivo electrophysiological recordings of VTA DA neuron activity or ventral hippocampal (vHPC) pyramidal neuron activity. MAM rats treated with POM demonstrated increased NOR in adulthood compared to no injection MAM rats, but not compared to vehicle-treated MAM rats. POM-treated MAM rats demonstrated normalized DA neuron population activity and vHPC pyramidal neuron activity compared to vehicle and no injection MAM rats in both late adolescence and adulthood. No significant differences were observed across treatment groups in SAL rats. These results suggest that peripubertal mGluR2/3 agonist administration can prevent the emergence of vHPC pyramidal neuron hyperactivity and increased DA neuron population activity in adult MAM rats. |
| Databáze: | OpenAIRE |
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