Sailaja A Goda1, Maciej Olszewski1, Joanna Piasecka1, Karolina Rejniak1, Miles A Whittington2, Stefan Kasicki1, Mark J Hunt3. 1. Laboratory of the Limbic System, Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093 Warsaw, Poland. 2. The Hull York Medical School, University of York, Heslington, York YO10 5DD, UK. 3. Laboratory of the Limbic System, Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093 Warsaw, Poland; The Hull York Medical School, University of York, Heslington, York YO10 5DD, UK.
Abstract
BACKGROUND: Altered activity of the nucleus accumbens (NAc) is thought to be a core feature of schizophrenia and animal models of the disease. Abnormal high frequency oscillations (HFO) in the rat NAc have been associated with pharmacological models of schizophrenia, in particular the N-methyl-d-aspartate receptor (NMDAR) hypofunction model. Here, we tested the hypothesis that abnormal HFO are also associated with a neurodevelopmental rat model. METHODS: Using prenatal administration of the mitotoxin methylazoxymethanol acetate (MAM) we obtained the offspring MAM rats. Adult MAM and Sham rats were implanted with electrodes, for local field potential recordings, in the NAc. RESULTS: Spontaneous HFO (spHFO) in MAM rats were characterized by increased power and frequency relative to Sham rats. MK801 dose-dependently increased the power of HFO in both groups. However, the dose-dependent increase in HFO frequency found in Sham rats was occluded in MAM rats. The antipsychotic compound, clozapine reduced the frequency of HFO which was similar in both MAM and Sham rats. Further, HFO were modulated in a similar manner by delta oscillations in both MAM and Sham rats. CONCLUSION: Together these findings suggest that increased HFO frequency represents an important feature in certain animal models of schizophrenia. These findings support the hypothesis that altered functioning of the NAc is a core feature in animal models of schizophrenia.
BACKGROUND: Altered activity of the nucleus accumbens (NAc) is thought to be a core feature of schizophrenia and animal models of the disease. Abnormal high frequency oscillations (HFO) in the rat NAc have been associated with pharmacological models of schizophrenia, in particular the N-methyl-d-aspartate receptor (NMDAR) hypofunction model. Here, we tested the hypothesis that abnormal HFO are also associated with a neurodevelopmental rat model. METHODS: Using prenatal administration of the mitotoxin methylazoxymethanol acetate (MAM) we obtained the offspring MAMrats. Adult MAM and Sham rats were implanted with electrodes, for local field potential recordings, in the NAc. RESULTS: Spontaneous HFO (spHFO) in MAMrats were characterized by increased power and frequency relative to Sham rats. MK801 dose-dependently increased the power of HFO in both groups. However, the dose-dependent increase in HFO frequency found in Sham rats was occluded in MAMrats. The antipsychotic compound, clozapine reduced the frequency of HFO which was similar in both MAM and Sham rats. Further, HFO were modulated in a similar manner by delta oscillations in both MAM and Sham rats. CONCLUSION: Together these findings suggest that increased HFO frequency represents an important feature in certain animal models of schizophrenia. These findings support the hypothesis that altered functioning of the NAc is a core feature in animal models of schizophrenia.
Authors: Jacek Wróbel; Władysław Średniawa; Gabriela Jurkiewicz; Jarosław Żygierewicz; Daniel K Wójcik; Miles Adrian Whittington; Mark Jeremy Hunt Journal: Sci Rep Date: 2020-11-04 Impact factor: 4.379