Low-dose digoxin enhances the anticonvulsive potential of carbamazepine and lamotrigine in chemo-induced seizures with different neurochemical mechanisms

"Non-antiepileptic" drugs have a strong potential as adjuvants in multidrug-resistant epilepsy treatment. In previous study the influence of low doses of digoxin, which do not affect the myocardium, on the anticonvulsant potential of classical commonly used anti-epileptic drugs under conditions of seizures, induced by pentylenetetrazole and maximal electroshock, has been investigated. The aim of the study was to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant potential of carbamazepine and lamotrigine in experimental seizures with different neurochemical mechanisms. Material and methods: A total of 192 random-bred male albino mice weighting 22–25 g were used. Carbamazepine and lamotrigine were administered intragastrically in conditionally effective (ED50) and sub-effective (½ ED50) doses: carbamazepine at doses of 100 and 50 mg/kg; lamotrigine at doses of 25 and 12.5 mg/kg. Digoxin was administered subcutaneously at a sub-cardiotonic dose of 0.8 mg/kg as an adjuvant to carbamazepine and lamotrigine in ½ ED50. Picrotoxin (2.5 mg/kg subcutaneously); thiosemicarbazide (25 mg/kg intraperitoneally); strychnine (1.2 mg/kg subcutaneously); camphor (1000 mg/kg intraperitoneally) were used as convulsant agents. Results: It was found that digoxin not only has its own permanent anticonvulsant effect on different models of paroxysms with different neurochemical mechanisms of development, but also significantly enhances the anticonvulsant potential of carbamazepine (to a lesser extent – lamotrigine) regardless of the pathogenesis of experimental paroxysms. Conclusion: Based on the results, it can be concluded that digoxin has a high potential as an adjuvant medicine in complex epilepsy treatment because it enhances the efficiency of low-dose traditional anticonvulsants carbamazepine and lamotrigine

Epilogue

In the closing chapter of this volume, the authors highlight conceptual, methodological, technical, and speculative issues that emerge from the collection and that they believe point to important future directions for the field of neuroaesthetics. One fundamental question that runs implicitly through the collection and is answered variously by the authors is what is meant by “aesthetics.” We note, too, opportunities for new lines of research that will significantly advance the models and applied relevance of neuroaesthetics. Such studies might address cross-cultural tests of neuroaesthetic theories, temporal dimensions of aesthetic engagement, multimodal experiences, neurochemical mechanisms, neuropsychological investigations of aesthetic experience, naturalistic experimental designs, and the impact of artificial intelligence and other technologies on our conceptions of art and creativity.

Combining transcranial brain stimulation and PET/SPECT molecular imaging

Transcranial brain stimulation (TMS) was introduced in 1985 by Barker and his colleagues. Since then, further improvements in technology have allowed additional applications and new stimulation protocols. In the last decade, while the use of TMS has expanded enormously in basic science as well as in the clinical scenario, the underlying neurophysiological or neurochemical mechanisms are still not fully understood. Positron emission tomography (PET) and single-photon emission computerized tomography (SPECT) are neuroimaging modalities utilized to investigate brain functions. In spite of their lower spatial and time resolution compared with functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), PET/SPECT have helped to elucidate some of the neurochemical mechanisms and neural plastic changes associated with TMS. In this chapter, we will provide an overview of these techniques, describing methodological details and application of TMS-PET/SPECT imaging in basic and clinical studies.

Possible Mechanisms of Hypnosis from an Interactional Perspective

In this paper, utilizing the interactional research paradigm developed by Éva Bányai, we discuss the hypnotic relationship from the viewpoint of interactional synchrony. Based on our three decades of empirical studies of an interactional paradigm, we propose the analogy between hypnosis and mother–child interaction. Hypnosis is considered as a potential corrective/reparative possibility when the real childhood experiences appear to be unfavourable. Possible neuroanatomical and neurochemical mechanisms are also suggested in the right hemispheric orbitofrontal cortex and central oxytocin system.

Cannabidiol modulation of hippocampal glutamate in early psychosis

Background: Emerging evidence supports the antipsychotic effect of cannabidiol, a non-intoxicating component of cannabis, in people with psychosis. Preclinical findings suggest that this antipsychotic effect may be related to cannabidiol modulating glutamatergic signalling in the brain. Aim: The purpose of this study was to investigate the effects of cannabidiol on the neurochemical mechanisms underlying psychosis. Methods: We investigated the effects of a single oral dose of cannabidiol (600 mg) in patients with psychosis, using a double-blind, randomised, placebo-controlled, repeated-measures, within-subject cross-over design. After drug administration, 13 patients were scanned using proton magnetic resonance spectroscopy to measure left hippocampal glutamate levels. Symptom severity was rated using the Positive and Negative Syndrome Scale 60 min before drug administration (pre-scan), and 270 min after drug administration (post-scan). Effects of cannabidiol on hippocampal glutamate levels, symptom severity, and correlations between hippocampal glutamate and symptoms were investigated. Results: Compared to placebo, there was a significant increase in hippocampal glutamate ( p=0.035), and a significantly greater decrease in symptom severity ( p=0.032) in the psychosis patients under cannabidiol treatment. There was also a significant negative relationship between post-treatment total Positive and Negative Syndrome Scale score and hippocampal glutamate ( p=0.047), when baseline Positive and Negative Syndrome Scale score, treatment (cannabidiol vs placebo), and interaction between treatment and glutamate levels were controlled for. Conclusions: These findings may suggest a link between the increase in glutamate levels and concomitant decrease in symptom severity under cannabidiol treatment observed in psychosis patients. Furthermore, the findings provide novel insight into the potential neurochemical mechanisms underlying the antipsychotic effects of cannabidiol.