Journal
NEUROBIOLOGY OF LEARNING AND MEMORY
Volume 146, Issue -, Pages 12-20Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nlm.2017.10.015
Keywords
Intranasal dopamine; DISC1; Novel object exploration; Memory; Attention; Animal model
Funding
- Heisenberg Fellowship [SO 1032/5-1]
- MC-ITN IN-SENS [607616]
- Medical Faculty of the Heinrich Heine University Dusseldorf [9772569]
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The Disrupted-in-Schizophrenia 1 (DISCI) gene has been associated with mental illnesses such as major depression and schizophrenia. The transgenic DISCI (tgDISC1) rat, which overexpresses the human DISCI gene, is known to exhibit deficient dopamine (DA) homeostasis. To ascertain whether the DISCI gene also impacts cognitive functions, 14-15 months old male tgDISC1 rats and wild-type controls were subjected to the novel object preference (NOP) test and the object-based attention test (OBAT) in order to assess short-term memory (1 h), long-term memory (24 h), and attention. Results: The tgDISC1 group exhibited intact short-term memory, but deficient long-term-memory in the NOP test and deficient attention-related behavior in the OBAT. In a different group of tgDISC1 rats, 3 mg/kg intranasally applied dopamine (IN-DA) or its vehicle was applied prior to the NOP or the OBAT test. IN-DA reversed cognitive deficits in both the NOP and OBAT tests. In a further cohort of tgDISC1 rats, post-mortem levels of DA, noradrenaline, serotonin and acetylcholine were determined in a variety of brain regions. The tgDISC1 group had less DA in the neostriatum, hippocampus and amygdala, less acetylcholine in neostriatum, nucleus accumbens, hippocampus, and amygdala, more serotonin in the nucleus accumbens, and less serotonin and noradrenaline in the amygdala. Conclusions: Our findings show that DISCI overexpression and misassembly is associated with deficits in long-term memory and attention-related behavior. Since behavioral impairments in tgDISC1 rats were reversed by IN-DA, DA deficiency may be a major cause for the behavioral deficits expressed in this model.
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