Addictive drug use or prescribed medicine abuse can cause psychosis. Some representative symptoms frequently elicited by patients with psychosis are hallucination, anhedonia, and disrupted executive functions. These psychoses are categorized into three classifications of symptoms: positive, negative, and cognitive. The symptoms of DIP are not different from the symptoms of schizophrenia, and it is difficult to distinguish between them. Due to this ambiguity of distinction between the DIP and schizophrenia, the DIP animal model has been frequently used as the schizophrenia animal model. However, although the symptoms may be the same, its causes are clearly different in that DIP is acquired and schizophrenia is heritable. Therefore, in this review, we cover several DIP models such as of amphetamine, PCP/ketamine, scopolamine, and LSD, and then we also address three schizophrenia models through a genetic approach with a new perspective that distinguishes DIP from schizophrenia.
Amphetamine ; Anhedonia ; Classification ; Executive Function ; Hallucinations ; Humans ; Lysergic Acid Diethylamide ; Models, Animal ; Psychotic Disorders* ; Schizophrenia ; Scopolamine Hydrobromide ; Substance-Related Disorders*

PURPOSE: Presenilins are functionally important components of γ-secretase, which cleaves a number of transmembrane proteins. Manipulations of PSEN1 and PSEN2 have been separately studied in Alzheimer disease (AD) and cancer because both involve substrates of γ-secretase. However, numerous clinical studies have reported an inverse correlation between AD and cancer. Interestingly, AD is a neurodegenerative disorder, whereas cancer is characterized by the proliferation of malignant cells. However, this inverse correlation in the PSEN double-knockout (PSEN dKO) mouse model of AD has been not elucidated, although doing so would shed light onto the relationship between AD and cancer. METHODS: To investigate the inverse relationship of AD and cancer under conditions of PSEN loss, we used the hippocampus of 7-month-old and 18-month-old PSEN dKO mice for a microRNA (miRNA) microarray analysis, and explored the tumorsuppressive or oncogenic role of differentially-expressed miRNAs. RESULTS: The total number of miRNAs that showed changes in expression level was greater at 18 months of age than at 7 months. Most of the putative target genes of the differentially-expressed miRNAs involved Cancer pathways. CONCLUSIONS: Based on literature reviews, many of the miRNAs involved in Cancer pathways were found to be known tumorsuppressive miRNAs, and their target genes were known or putative oncogenes. In conclusion, the expression levels of known tumor-suppressive miRNAs increased at 7 and 18 months, in the PSEN dKO mouse model of AD, supporting the negative correlation between AD and cancer.
Alzheimer Disease* ; Animals ; Hippocampus ; Humans ; Infant ; Mice* ; Microarray Analysis ; MicroRNAs ; Neurodegenerative Diseases ; Oncogenes ; Presenilins

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.