RESUMEN
Acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. Recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. However, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter tracts that underpin the neuropathology of schizophrenia. Thus, the present study aimed to expand on previous investigations by examining causal effects of repeated ketamine exposure on white matter integrity in a non-human primate model. Ketamine or saline (control) was administered intravenously for 3 months to male adolescent cynomolgus monkeys (n = 5/group). Diffusion tensor imaging (DTI) experiments were performed and tract-based spatial statistics (TBSS) was used for data analysis. Fractional anisotropy (FA) was quantified across the whole brain. Profoundly reduced FA on the right side of sagittal striatum, posterior thalamic radiation (PTR), retrolenticular limb of the internal capsule (RLIC) and superior longitudinal fasciculus (SLF), and on the left side of PTR, middle temporal gyrus and inferior frontal gyrus were observed in the ketamine group compared to controls. Diminished white matter integrity found in either fronto-thalamo-temporal or striato-thalamic connections with tracts including the SLF, PTR, and RLIC lends support to similar findings from DTI studies on schizophrenia in humans. This study suggests that chronic ketamine exposure is a useful pharmacological paradigm that might provide translational insights into the pathophysiology and treatment of schizophrenia.
RESUMEN
This study examined the heat shock protein 70 (HSP70) expression in hippocampal CA3 subfield of rats in different chronic stress models. The chronic restraint stress (CRS) and the chronic mild stress (CMS) models were used in this study. Observation of exploratory behavior in an open field test indicated stress level. The expression of HSP70 in hippocampal CA3 subfield was measured by immunohistochemical methods. The results showed that the number of quadrant crossing in both CRS and CMS groups decreased more than that of the control (P < 0.01). CRS group crossing decreased more than CMS group. Damage in the hippocampus of the CMS group occurred later and to a less extent than that of the CRS group. Compared with CMS group, the expression of HSP70 was greater in the CRS group. Moreover, increased stress duration enhanced these effects. These results show that the CRS model affects both exploratory behavior and HSP70 expression in the hippocampus more dramatically than the CMS model.