Downregulation of 5-hydroxytryptamine7 receptor in the medial prefrontal cortex ameliorates impulsive actions in animal models of schizophrenia

Abstract

R mRNA in the mPFC was significantly decreased to 5-Hydroxytryptamine7 (5-HT7) receptors in the medial prefrontal cortex (mPFC) play a critical role in complex cognitive impairment in schizophrenia. The mouse model of schizophrenia was established through the neonatal administration of phencyclidine (nPCP). Recombinant adeno-associated virus-mediated gene knockdown was used to investigate the role of mPFC 5-HT7 receptor in the schizophrenia-like symptoms in mice. Under baseline conditions in the 5-choice serial reaction time task (5-CSRTT), nPCP produced a significant attentional impairment that was exacerbated when mice were tested under LITI. Premature and perseverative responding in nPCP mice were both increased, thus suggesting deficits in inhibitory response control. The deficits in attentional performance and premature responding of nPCP mice were improved or fully rescued by 5-HT7 receptor downregulation under heavy perceptual load. Downregulation of the 5-HT7 receptor in the mPFC ameliorated spatial working memory and had no effects on nPCP-induced impairments in recognition memory and MA-induced hyperlocomotion. These results suggest that 5-HT7 receptor is involved in the cognitive outcomes of schizophrenia-like symptoms similar to humans. Downregulation of the 5-HT7 receptor in the mPFC exert complex effects in a mouse model of schizophrenia and may be of benefit in treating schizophrenia-related impulsive actions.