No abstract

Mephedrone is a widely used drug of abuse, exerting its effects by interacting with monoamine transporters. Although this mechanism has been widely studied heretofore, little is known about the involvement of glutamatergic transmission in mephedrone effects. In this study, we comprehensively evaluated glutamatergic involvement in rewarding effects of mephedrone using an interdisciplinary approach including (1) behavioural study on effects of memantine (non-selective NMDA antagonist) on expression of mephedrone-induced conditioned place preference (CPP) in rats; (2) evaluation of glutamate concentrations in the hippocampus of rats following 6 days of mephedrone administration, using in vivo magnetic resonance spectroscopy (MRS); and (3) determination of glutamate levels in the hippocampus of rats treated with mephedrone and subjected to MRS, using ion-exchange chromatography. In the presented research, we confirmed priorly reported mephedrone-induced rewarding effects in the CPP paradigm and showed that memantine (5 mg/kg) was able to reverse the expression of this effect. MRS study showed that subchronic mephedrone administration increased glutamate level in the hippocampus when measured in vivo 24 h (5 mg/kg, 10 mg/kg and 20 mg/kg) and 2 weeks (5 mg/kg and 20 mg/kg) after last injection. Ex vivo chromatographic analysis did not show significant changes in hippocampal glutamate concentrations; however, it showed similar results as obtained in the MRS study proving its validity. Taken together, the presented study provides new insight into glutamatergic involvement in rewarding properties of mephedrone.

The work describes the physical basis of the chemical exchange saturation transfer (CEST) technique; it presents the beginnings of the implementation of the method and its possible applications. The principles of correct data acquisition and possible solutions used during the design of the CEST sequence are shown. The main problems related to data analysis are indicated, and an example Z-spectrum from in vivo study of the rat brain is introduced. Furthermore, the parameters related to spectrum analyses such as magnetisation transfer asymmetry (MTRasym) and amide proton transfer asymmetry (APTasym) are presented. In the following part, different types of the CEST method often mentioned in the literature are discussed. Subsequently, the possible applications of the CEST method in both clinical and experimental practice are described.

The intestinal microbiome composition and dietary supplementation with psychobiotics can result in neurochemical alterations in the brain, which are possible due to the presence of the brain–gut–microbiome axis. In the present study, magnetic resonance spectroscopy (MRS) and behavioural testing were used to evaluate whether treatment with Lacticaseibacillus rhamnosus JB-1 (JB‑1) bacteria alters brain metabolites’ levels and behaviour during continuous exposure to chronic stress. Twenty Wistar rats were subjected to eight weeks of a chronic unpredictable mild stress protocol. Simultaneously, half of them were fed with JB-1 bacteria, and the second half was given a daily placebo. Animals were examined at three-time points: before starting the stress protocol and after five and eight weeks of stress onset. In the elevated plus maze behavioural test the placebo group displayed increased anxiety expressed by almost complete avoidance of exploration, while the JB-1 dietary supplementation mitigated anxiety which resulted in a longer exploration time. Hippocampal MRS measurements demonstrated a significant decrease in glutamine + glutathione concentration in the placebo group compared to the JB-1 bacteria-supplemented group after five weeks of stress. With the progression of stress the decrease of glutamate, glutathione, taurine, and macromolecular concentrations were observed in the placebo group as compared to baseline. The level of brain metabolites in the JB-1-supplemented rats were stable throughout the experiment, with only the taurine level decreasing between weeks five and eight of stress. These data indicated that the JB-1 bacteria diet might stabilize levels of stress-related neurometabolites in rat brain and could prevent the development of anxiety/depressive-like behaviour.

The aim of the work was to share the practical experience of preclinical and clinical proton magnetic resonance spectroscopy (1 HMRS) studies conducted using a 7-Tesla magnetic field strength scanner, taking into account the specificity of both settings in the context of translational research. Material and methods: 1 HMRS volunteer studies conducted using a Discovery 950 GE 7T scanner, were carried out with PRESS sequence, and a VOI measuring 2.0 × 2.0 × 2.0 cm 3 placed in the white matter at the parietal occipital lobe. Rodent spectra obtained using a 7T Bruker were measured with PRESS, with a VOI 2.0 × 2.0 × 5.5 mm 3 placed over the hippocampus. Results: 1 HMRS data from humans and rats show that the brain spectra obtained in the same field are characterised by a similar neurochemical structure and spectral resolution. Spectra obtained from rats demonstrate the following metabolites: NAA, Glu, Gln, Ins, Cho, Cr, PCr, Tau, GABA, Lac, NAAG, and Asp. In turn, spectra from humans allowed estimation of the following metabolites: Ala, NAA, Glu, Gln, Ins, Cho, Cr, PCr, Tau, GABA, Lac, NAAG, and Asp. Signals from Gln, Glu with chemical shift around 2.4 ppm, from Cr, PCr, and GABA at 3 ppm, and signals from Cho and Tau at approximately 3.2 ppm, can be properly separated and estimated both in humans and in rats. Conclusions: These results are promising in terms of broadening the knowledge of many neurological diseases by inducing them on animal models and then transferring this knowledge to clinical practice. In spite of this, important distinctions in the technical aspects and methodological differences of high-field 1 HMRS in both preclinical and clinical conditions should be taken into account.