Repeated transcranial direct current stimulation induces behavioral, metabolic and neurochemical effects in rats on high-calorie diet

Due to its high prevalence, obesity is considered an epidemic, which stimulated research on non-invasive methods to reduce excess body fat. Transcranial direct current stimulation (tDCS) is a non-invasive technique used to modulate the activity of cerebral cortex, which has already found increasing interest in medicine as a promising methodology. The aim of this study was to analyze the impact of tDCS on feeding behavior, metabolic abnormalities and neurotransmitters in certain brain areas involved in appetite control of obese rats. The male Wistar rats were divided into five subgroups depending on consumed diet effect (lean, obese) and tDCS type (anodal, cathodal, sham, and no stimulation). Two 10-min daily sessions of tDCS for 8 consecutive days of the study were applied. Rats subjected to active tDCS (anodal right or cathodal left of the prefrontal cortex) had reduced appetite and showed lesser body weight gain than the animals subjected to sham procedure or those receiving no stimulation at all. Furthermore, tDCS contributed to reduction of epididymal fat pads and to a decrease in blood concentration of leptin. Neurochemical examination revealed that tDCS modulated serotonin pathways of the reward-related brain areas and contributed to a significant decrease in the density of D2 but not D1 dopamine receptors in the dorsal striatum, recorded 5 h after the last stimulation. No significant effect of tDCS on dopamine and it's metabolites in examined brain regions was observed. It seems that the hypothalamus was not affected by tDCS application as no changes in measured neurotransmitters were detected at any examined time point. However, these results do not exclude the possibility of the delayed response of the monoamines in the examined brain areas to tDCS application. Altogether, these findings imply that repeated tDCS of the prefrontal cortex may change feeding behavior of obese rats. Either right anodal or left cathodal tDCS were sufficient to decrease food intake, to reduce body adiposity and to normalize other metabolic anomalies. These beneficial effects can be at least partially explained by changes in serotoninergic and in lesser extent dopaminergic system activity within some brain areas belonging to reward system

Study of a mechanism responsible for potential antidepressant activity of EMD 386088, a 5-HT_6 partial agonist in rats

It was shown that 5-HT(6) receptor agonists can exert pharmacological activity due to various modifications in monoamines’ level and metabolism activity in rats’ brain structures. This finding was correlated with antidepressant- or anxiolytic-like properties of these compounds. The study was designed to establish a possible mechanism of the antidepressant-like activity of the partial 5-HT(6) receptor agonist EMD386088 (5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole hydrochloride) in rats. The concentrations of monoamines (dopamine (DA), noradrenaline (NA), and serotonin (5-HT)) and the rate of their metabolism were measured ex vivo in the brain structures (hippocampus, nucleus accumbens, striatum) using high-performance liquid chromatography (HPLC). The rats were killed after the forced swim test (FST); the collected tissue samples were used to ex vivo experiments. The potency of EMD386088 to blockade dopamine transporter (DAT) was tested in a functional in vitro study. FST was used to assess the involvement of D(1)- and D(2)-like receptor subfamilies in antidepressant-like properties of EMD386088. Neurochemical data from ex vivo experiments showed that antiimmobility activity of EMD386088 may be connected with the activation of dopaminergic system, while neither noradrenergic nor serotonergic ones are involved in its effect. EMD386088 also possesses a significant affinity for DAT which may be a mechanism in the abovementioned effect. Behavioral data seem to confirm the importance of dopaminergic system activation in antidepressant-like activity of EMD386088, since this effect, observed in the FST, was abolished by the preferential D(1)- and D(2)-like receptor subfamily antagonists SCH23390 and sulpiride, respectively. Dopaminergic system is involved in antidepressant-like activity of EMD386088