The effect of magnesium sulfate on memory and anxiety-like behavior in a rat model: an investigation of its neuronal molecular mechanisms.

BACKGROUND: Anxiety is an adaptive response to potentially threatening conditions. Excessive and uncontrolled anxiety responses become nonadaptive and cause anxiety disorders. To better understand the anxiety-modulating effects of Mg sulfate, behavioral test batteries in the assessment of anxiety and learning and memory functions were performed simultaneously over a time period. This study also examines the effects of Mg sulfate compared to diazepam, an anxiolytic drug with amnestic effects on anxiety-like behavior, as well as possible oxidative-nitrosative stress and hippocampal changes in male rats exposed to predator odor. METHODS: Young adult Sprague-Dawley male rats were used. The rats were assessed using a comprehensive neurobehavioral test battery consisting of novel object recognition, open field, and successive alleys tasks. Anxiety was induced by cat odor, and diazepam and Mg were used as study drugs. Of the frontal cortex and hippocampus, the state of total oxidant and antioxidant and NO levels and histological examination of hippocampal CA1, CA2, CA3, and DG regions were performed. RESULTS: Diazepam- and Mg-treated rats showed an improvement in anxiety-related behavior to predator odors. Furthermore, Mg treatment alleviated some of the increasing oxidative stress in the frontal cortex and hippocampus of rats, while diazepam treatment in particular enhanced hippocampal oxidant and antioxidant activity. In addition, brain NO increase induced by animal odor exposure or diazepam treatment was ameliorated by Mg administration. CONCLUSIONS: Overall, our work suggests that Mg had a partial anxiolytic effect on anxiety-like behaviors, although not as much as diazepam, and this effect varied depending on the dose. Mg treatment might counteract increased oxidative stress and elevated NO levels in the brain.

Adrenergic receptor system as a pharmacological target in the treatment of epilepsy (Review).

Epilepsy is a complex and common neurological disorder characterized by spontaneous and recurrent seizures, affecting ~75 million individuals worldwide. Numerous studies have been conducted to develop new pharmacological drugs for the effective treatment of epilepsy. In recent years, numerous experimental and clinical studies have focused on the role of the adrenergic receptor (AR) system in the regulation of epileptogenesis, seizure susceptibility and convulsions. α1-ARs (α1A, α1B and α1D), α2-ARs (α2A, α2B and α2C) and ß-ARs (ß1, ß2 and ß3), known to have convulsant or anticonvulsant effects, have been isolated. Norepinephrine (NE), the key endogenous agonist of ARs, is considered to play a crucial role in the pathophysiology of epileptic seizures. However, the effects of NE on different ARs have not been fully elucidated. Although the activation of some AR subtypes produces conflicting results, the activation of α1, α2 and ß receptor subtypes, in particular, produces anticonvulsant effects. The present review focuses on NE and ARs involved in epileptic seizure formation and discusses therapeutic approaches.

Daily life affective dynamics as transdiagnostic predictors of mental health symptoms: An ecological momentary assessment study.

BACKGROUND: Affective dynamics have been identified as a correlate of a broad span of mental health issues, making them key candidate transdiagnostic factors. However, there remains a lack of knowledge about which aspects of affective dynamics - especially as they manifest in the course of daily life - relate to a general risk for mental health issues versus specific symptoms. METHODS: We leverage an ecological momentary assessment (EMA) study design with four measures per day over a two-week period to explore how negative affect levels, inertia, lability, and reactivity to provocation and stress in the course of daily life relate to mental health symptoms in young adults (n = 256) in the domains of anxiety, depression, psychosis-like symptoms, behaviour problems, suicidality, and substance use. RESULTS: Dynamic structural equation modelling (DSEM) suggested that negative affect levels in daily life were associated with depression, anxiety, indirect and proactive aggression, psychosis, anxiety, and self-injury; negative affective lability was associated with depression, physical aggression, reactive aggression, suicidal ideation, and ADHD symptoms; negative affective inertia was associated with depression, anxiety, physical aggression, and cannabis use; and emotional reactivity to provocation was related to physical aggression. LIMITATIONS: The cross-sectional design, the limited span of mental health issues included, and the convenience nature and small size of the sample are limitations. CONCLUSIONS: Findings suggest that a subset of mental health symptoms have shared negative affective dynamics patterns. Longitudinal research is needed to rigorously examine the directionality of the effects underlying the association between affective dynamics and mental health issues.

Pathways from childhood trauma to aberrant salience: A structural equation approach to mentalization model.

OBJECTIVE: The aim of this study was to explore the relationship between affective disturbances and aberrant salience in the context of childhood trauma, attachment, and mentalization in an analogue study. METHODS: Using a cross-sectional design, an online community sample completed self-report measures of key variables. Structural equation modelling was used to test childhood trauma's influence on aberrant salience via a set of intermediate risk factors (depression, negative schizotypy, and insecure attachment). These intermediate risk factors were assumed to lead to the proximal risk factors of aberrant salience (i.e., disorganized schizotypy and disorganized attachment) depending on the vulnerability of mentalizing capacity to elevated stress. RESULTS: The sample (N = 1263) was 78% female and aged between 18 and 35 years. The tested models closely fitted the observed data, revealing significant pathways from childhood trauma to aberrant salience via the hypothesized pathways. The direct effect of childhood trauma on aberrant salience was significant. CONCLUSION: Findings suggest that the pathway to aberrant salience may be characterized by disorganization of self-state and intersubjectivity as a function of diminishment in mentalizing ability. This may relate to changes in attachment organization and socio-cognitive capacity, which could constitute possible risk factors signalling development of aberrant salience.

Aspirin attenuates morphine antinociceptive tolerance in rats with diabetic neuropathy by inhibiting apoptosis in the dorsal root ganglia.

Morphine is a drug used in chronic pain such as diabetic neuropathy, but the development of tolerance to its antinociceptive effect is an important clinical problem. Aspirin is an analgesic and antiapoptotic drug used in combination with morphine as an adjuvant in diabetic neuropathy. Our aim in this study was to investigate the effects of aspirin on morphine-induced neuronal apoptosis and analgesic tolerance in rats with diabetic neuropathy. The antinociceptive effects of aspirin (50 mg/kg) and morphine (5 mg/kg) were evaluated by thermal pain tests. Streptozotocin (65 mg/kg) was injected intraperitoneally to induce diabetic neuropathy. To evaluate apoptosis, ELISA kits were used to measure caspase-3, Bax and Bcl-2 levels. Apoptotic cells were detected histologically by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. Study results indicate that prior administration of aspirin to diabetic rats significantly increased the antinociceptive efficacy of morphine compared to morphine alone. Thermal pain tests showed that aspirin significantly reduced morphine tolerance in rats with diabetic neuropathy. Biochemical analysis revealed that aspirin significantly decreased the levels of pro-apoptotic proteins, caspase-3 and Bax, while increasing the anti-apoptotic Bcl-2 in DRG neurons. Semiquantitative scoring demonstrated that aspirin provided a significant reduction in apoptotic cell counts in diabetic rats. In conclusion, these data suggested that aspirin attenuated morphine antinociceptive tolerance through anti-apoptotic activity in diabetic rat DRG neurons.

Blockade of orexin receptor type-1 by SB-334867 and activation of orexin receptor type-2 attenuate morphine tolerance in rats.

Purpose: The interaction of orexinergic neurons with the opioidergic system and their effects on morphine analgesia and tolerance have not been fully elucidated. The purpose of the study was to evaluate the effects of the orexin-1 and orexin-2 receptor (OX1R and OX2R) agonist and antagonist on morphine analgesia and tolerance in rats. Material and methods: A total of 90 Wistar albino male rats weighing 180-220 g were used in the experiments. To induce morphine tolerance, rats were injected with a single dose of morphine (50 mg kg-1, s.c.) for 3 days. Morphine tolerance was assessed on day 4 in randomly selected rats by analgesia tests. In order to evaluate morphine tolerance situation, orexin-A, SB-334867, orexin-B and TCS OX2 29 were administered together with morphine for 3 days. The analgesic effects of orexin-A (10 µg kg-1), OXR1 antagonist SB-334867 (10 mg kg-1), OXR2 agonist orexin-B (15 µg kg-1), OXR2 antagonist TCS OX2 29 (0.5 mg kg-1) and morphine (5 mg kg-1) were measured at 15 or 30-min intervals by tail-flick and hot-plate antinociceptive tests. Results: The results suggested that the combination of orexin-1 receptor antagonist SB-334867 and orexin-B with morphine significantly increased the analgesic effect compared to morphine-tolerant rats. In addition, administration of orexin-A and -B alone showed significant analgesic effects compared to the saline group. However, co-administration of orexin-A and -B with morphine did not increase the analgesic efficacy of morphine. Conclusions: The results of this study demonstrated that co-administration of SB-334867 and orexin-B with morphine attenuated morphine tolerance. Further studies are needed to elucidate the details of the interaction between orexin receptors and the opioidergic system.

Metformin prevents morphine-induced apoptosis in rats with diabetic neuropathy: a possible mechanism for attenuating morphine tolerance.

Morphine is a drug of choice for the treatment of severe and chronic pain, but tolerance to the antinociceptive effect limits its use. The development of tolerance to morphine has recently been associated with neuronal apoptosis. In this study, our aim was to investigate the effects of metformin on morphine-induced neuronal apoptosis and antinociceptive tolerance in diabetic rats. Three days of cumulative dosing were administered to establish morphine tolerance in rats. The antinociceptive effects of metformin (50 mg/kg) and test dose of morphine (5 mg/kg) were considered at 30-min intervals by thermal antinociceptive tests. To induce diabetic neuropathy, streptozotocin (STZ, 65 mg/kg) was injected intraperitoneally. ELISA kits were used to measure caspase-3, bax, and bcl-2 levels from dorsal root ganglion (DRG) tissue. Semi-quantitative scoring system was used to evaluate apoptotic cells with the the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. The findings suggest that co-administration of metformin with morphine to diabetic rats showed a significant increase in antinociceptive effect compared to morphine alone. The antinociceptive tests indicated that metformin significantly attenuated morphine antinociceptive tolerance in diabetic rats. In addition, metformin decreased the levels of apoptotic proteins caspase 3 and Bax in DRG neurons, while significantly increased the levels of antiapoptotic Bcl-2. Semi-quantitative scoring showed that metformin provided a significant reduction in apoptotic cell counts in diabetic rats. These data revealed that metformin demonstrated antiapoptotic activity in diabetic rat DRG neurons and attenuated morphine tolerance. The antiapoptotic activity of metformin probably plays a significant role in reducing morphine tolerance.

The 5-HT7 receptor antagonist SB-269970 alleviates seizure activity and downregulates hippocampal c-Fos expression in pentylenetetrazole-induced kindled rats.

OBJECTIVES: Recently, studies have demonstrated that serotonin type 7 receptors (5-HT7) have conflincting effects on neuronal excitability in different brain regions. However, the effect of 5-HT7 on seizures has not been exactly elucidated yet. Therefore, our aim in this study was to investigate the effects of 5-HT7 antagonist SB-269970 on pentylenetetrazole (PTZ) induced fully kindled rats. METHODS: In the study, 32 adult male Wistar Albino rats (weighing 220-260 g) were used. Rats were injected with PTZ (35 mg/kg) intraperitoneally every other day to generate kindling model. 5-CT (0.1 mg/kg) and SB-269970 (1 mg/kg) were administered 30 min before acute seizure induction with PTZ (35 mg/kg). Seizure stages were determined according to the Racine scale. After electrocorticography (ECoG) recordings of seizure-induced rats were obtained, the animals were sacrificed by decapitation. The hippocampal GABA levels were determined by ELISA kit and the number of c-Fos positive neurons in the hippocampal dentate gyrus (DG), CA1 and CA3 areas were measured by immunohistochemical method. RESULTS: The results showed that SB-269970 reduced the number of spikes, percent seizure duration and duration of generalized tonic-clonic seizures (dGTCS), while increasing the onset time of generalized tonic-clonic seizures (oGTCS). The hippocampal GABA levels were significantly increased in the SB-269970 group compared with the PTZ group. In addition, SB-269970 reduced the number of c-Fos positive cells in hippocampal CA1 area. DISCUSSION: 5-HT7 antagonist SB-269970 displays anticonvulsant effects on PTZ-induced seizures in fully kindled rats and these effects may be related to GABAergic activity in the hippocampus.

The Anticonvulsant Effects of Alpha-2 Adrenoceptor Agonist Dexmedetomidine on Pentylenetetrazole-Induced Seizures in Rats.

Alpha2-adrenoreceptor (α2-AR) is a noradrenergic receptor that is frequently studied for modulation of seizure activity. However, the precise role of this receptor agonists in regulating seizure activity is still unclear. Our aim in this study was to investigate the effects of α2-AR agonist dexmedetomidine (DEX) and atipamezole (α2-AR antagonist, ATI) on seziures in rats. In the study, 32 adult male Wistar Albino rats (weighing 220-260 g) were used. To induce seizures in rats, pentylenetetrazole (PTZ, 35 mg/kg) was injected intraperitoneally (i.p.) and seizure stages were determined according to the Racine scale. After induction of seizures, DEX (0.1 mg/kg, i.p.) and ATI (1 mg/kg, i.p.) were administered to rats and their effects determined on seizures. GABA levels of the brain hippocampal tissue sample were measured using an ELISA kit and c-Fos positive cells of the dentate gyrus and hippocampal regions were quantitatively analyzed with Image J software. The results showed that DEX decreased the seizure stages according to the Racine scale, significantly prolonged the onset time of first myoclonic jerk (FMJ) and reduced the number of spikes and percentage seizure duration (p < 0.05). In contrast, ATI increased the seizure stage, the number of spikes and percentage seizure duration. The hippocampal GABA level was significantly decreased in rats with only PTZ injection (p < 0.05). In addition, DEX reduced the number of c-Fos positive cells in dentate gyrus and the hippocampal CA1 and CA3 regions. In conclusion, our findings showed that α2-AR agonist DEX had a reducing activity on PTZ-induced seizure, while α2-AR antagonist ATI facilitated seizure formation.

The Effects of Proton Pump Inhibitors (Pantoprazole) on Pentylenetetrazole-Induced Epileptic Seizures in Rats and Neurotoxicity in the SH-SY5Y Human Neuroblastoma Cell Line.

Recent studies have shown that proton pump inhibitors have positive effects on the nervous system. However, its effect on epileptic seizure and neuronal damage are still unclear. In this study, it was aimed to investigate the effect of pantoprazole on pentylenetetrazole-induced epileptic seizures in rats and neurotoxicity in the SH-SY5Y cell line. Animals were divided into three groups: control, saline (1 mL/kg serum physiologic), and pantoprazole (10 mg/kg). Pentylenetetrazole (45 mg/kg) was given to induce a seizure and a passive avoidance test trial was carried out to evaluate memory function. 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, and brain-derived neurotrophic factor (BDNF) levels were measured in the brain by commercial kits. SH-SY5Y cells were treated with saline or pantoprazole for one hour, and then pentylenetetrazole (30 µm) was added to the medium to induce neurotoxicity. After 24 h, cell viability, total antioxidant, total oxidant status, and apoptosis were measured in SH-SY5Y cells. It was found that pantoprazole treatment postponed epileptic seizure onset, protected memory, reduced 8-OHdG, caspase-3, and also increased BDNF in the brain. In addition, it blocked pentylenetetrazole toxicity, apoptosis, increased antioxidant, and decreased oxidant status in SH-SY5Y cells. Pantoprazole significantly improved seizure, oxidative stress, and apoptosis. Thus, pantoprazole could be used as a supportive therapeutic agent in epilepsy.

Ghrelin receptor agonist hexarelin attenuates antinociceptive tolerance to morphine in rats.

Ghrelin, a peptide hormone released from the gastric endocrine glands, shows analgesic activity apart from its various physiological effects. Nevertheless, the effects of ghrelin receptor (GHS-R) agonists on morphine analgesia and tolerance have not yet been elucidated. The purpose of this study was to evaluate the effects of the ghrelin receptor agonist hexarelin and antagonist [d-Lys3]-GHRP-6 on morphine antinociception and tolerance in rats. A total of 104 Wistar albino male adult rats (weighing approximately 220-240 g) were used in the experiments. To induce morphine tolerance, a three-day cumulative dose regimen was used in the rats. Then, randomly selected rats were evaluated for morphine tolerance on day 4. The analgesic effects of hexarelin (0.2 mg·kg-1), [d-Lys3]-GHRP-6 (10 mg·kg-1), and morphine (5 mg·kg-1) were measured at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. The findings suggest that hexarelin in combination with morphine attenuates analgesic tolerance to morphine. On the other hand, ghrelin receptor antagonist [d-Lys3]-GHRP-6 has no significant analgesic activity on the morphine tolerance in analgesia tests. Furthermore, co-administration of hexarelin and morphine increases the analgesic effect. In conclusion, these data indicate that administration of GHS-R agonist hexarelin with morphine enhances the antinociception and attenuates morphine tolerance.

The effects of salmon calcitonin on epileptic seizures, epileptogenesis, and postseizure hippocampal neuronal damage in pentylenetetrazole-induced epilepsy model in rats.

Epilepsy is one of the most common neurological disorders that severely affect the life quality of many people worldwide. Excitatory-inhibitory mechanisms, oxidative stress, and also inflammation systems have been implicated in the pathogenesis of epilepsy. Recent studies have shown that salmon calcitonin (sCT) has positive effects on the nervous system. However, its relation with epilepsy is still unclear. This study aimed to investigate the effect of sCT on epileptic seizures, epileptogenesis, and postseizure hippocampal neuronal damage in pentylenetetrazole (PTZ)-induced epilepsy model in rats. The study was performed in two steps. In the first step, the effect of sCT on epileptic seizures was evaluated by using electroencephalography (EEG) in fully kindled rats. In the second step, the effect of sCT on epileptogenesis was evaluated by using the kindling process. Glutamate and gamma-aminobutyric acid (GABA), thiobarbituric acid reactive substance (TBARS), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1 ß), and interleukin 6 (IL-6) were measured in the second group in the brain and serum. Hippocampal regions were stained with hematoxylin-eosin and toluidine blue to evaluate hippocampal neuronal damage histopathologically. Salmon calcitonin showed an antiepileptic effect in fully kindled rats and also prevented the development of epileptogenesis in the kindling process. Besides, sCT decreased glutamate and increased GABA levels. Furthermore, it reduced TBARS levels and increased SOD and CAT levels. On the other hand, it decreased TNF-α levels, IL-1 ß levels, and IL-6 levels. Histopathologically, sCT decreased neuronal damage in all hippocampal regions. Our findings are the first preclinical report to show the positive effect of sCT on epileptic seizures and epileptogenesis. Further investigation is required to answer the questions raised about the probable mechanisms involved.

Response to Comment on "Dry reforming of methane by stable Ni-Mo nanocatalysts on single-crystalline MgO".

Hu and Ruckenstein state that our findings were overclaimed and not new, despite our presentation of evidence for the Nanocatalysts on Single Crystal Edges (NOSCE) mechanism. Their arguments do not take into account fundamental differences between our Ni-Mo/MgO catalyst and their NiO/MgO preparations.

The Role of the Cannabinoid System in Opioid Analgesia and Tolerance.

Opioid receptor agonist drugs, such as morphine, are very effective for treating chronic and severe pain; but, tolerance can develop with long-term use. Although there is a lot of information about the pathophysiological mechanisms of opioid tolerance, it is still not fully clarified. Suggested mechanisms for opioid tolerance include opioid receptor desensitisation, reduction of sensitivity G-proteins, activation of Mitogen-Activated Protein Kinase (MAPK), altered intracellular signaling pathway including nitric oxide, and activation of mammalian Target of Rapamycin (mTOR). One way to reduce opioid tolerance and increase the analgesic potential is to use low doses. Combination of cannabinoids with opioids has been shown to manifest the reduction of the opioid dose. Experimental studies revealed an interaction of the endocannabinoid system and opioid antinociception. Cannabinoid and opioid receptor systems use common pathways in the formation of analgesic effect and demonstrate their activity via G Protein Coupled Receptors (GPCR). Cannabinoid drugs modulate opioid analgesic activity at a number of distinct levels within the cell, ranging from direct receptor associations to post-receptor interactions through shared signal transduction pathways. This review summarizes the data indicating that with combining cannabinoids and opioids drugs may be able to produce long-term analgesic effects, while preventing the opioid analgesic tolerance.

Dry reforming of methane by stable Ni-Mo nanocatalysts on single-crystalline MgO.

Large-scale carbon fixation requires high-volume chemicals production from carbon dioxide. Dry reforming of methane could provide an economically feasible route if coke- and sintering-resistant catalysts were developed. Here, we report a molybdenum-doped nickel nanocatalyst that is stabilized at the edges of a single-crystalline magnesium oxide (MgO) support and show quantitative production of synthesis gas from dry reforming of methane. The catalyst runs more than 850 hours of continuous operation under 60 liters per unit mass of catalyst per hour reactive gas flow with no detectable coking. Synchrotron studies also show no sintering and reveal that during activation, 2.9 nanometers as synthesized crystallites move to combine into stable 17-nanometer grains at the edges of MgO crystals above the Tammann temperature. Our findings enable an industrially and economically viable path for carbon reclamation, and the "Nanocatalysts On Single Crystal Edges" technique could lead to stable catalyst designs for many challenging reactions.

The effects of extremely low-frequency pulsed electromagnetic fields on analgesia in the nitric oxide pathway.

There is growing interest in the effects of extremely low-frequency electromagnetic fields on mechanisms in biological organisms. This study's goal is to determine the role of the Nitiric Oxide (NO) pathway for thermal pain by intentionally interfering with it using a pulsed electromagnetic field generated by an extremely low-frequency alternating current (ELF-PEMF) in combination with BAY41-2272 (sGC activator), NOS inhibitor l-NAME, and NO donor l-arginine. This study included 72 adult male Wistar albino rats (mean weight of 230 ±â€¯12 g). The rats were kept at room temperature (22 ±â€¯2 °C) in a 12-h light/dark cycle and in a room with sound insulation. PEMF (50 Hz, 5 mT) were applied four times a day for 30 min and at 15-min intervals for 15 days. Analgesic effects were assessed with tail-flick and hot-plate tests. Before the tests, NO donor l-arginine (300 mg/kg), sGC activator BAY41-2272 (10 mg/kg), and NOS inhibitor l-name (40 mg/kg) were injected intraperitoneally into rats in six randomly-selected groups. The maximum analgesic effect of a 5 mT electromagnetic field was on day 7. PEMF significantly increased the analgesia effect when the functioning of the NO pathway was ensured with l-arginine, which is a NO donor, and BAY41-2271, which is the intracellular receptor and sGC activator. However, there was no difference between rats treated with PEMF and the NOS inhibitor l-NAME as compared to rats only treated with PEMF. In conclusion, PEMF generate analgesia by activating the NO pain pathway.

Effects of 5-HT1 and 5-HT 2 Receptor Agonists on Electromagnetic Field-Induced Analgesia in Rats.

Much evidence demonstrates the antinociceptive effect of magnetic fields (MFs). However, the analgesic action mechanism of the electromagnetic field (EMF) is not exactly understood. The aim of the present study was to investigate the effects of 5-HT1 and 5-HT2 receptor agonists (serotonin HCl and 2,5-dimethoxy-4-iodoamphetamine [DOI] hydrochloride) on EMF-induced analgesia. In total, 66 adult male Wistar albino rats with an average body mass of 225 ± 13 g were used in this study. The animals were subjected to repeated exposures of alternating 50 Hz and 5 mT EMF for 2 h a day for 15 days. Prior to analgesia tests, serotonin HCl (5-HT1 agonist) 4 mg/kg, WAY 100635 (5-HT1 antagonist) 0.04 mg/kg, DOI hydrochloride (5-HT2 receptor agonist) 4 mg/kg, and SB 204741 (5-HT2 antagonist) 0.5 mg/kg doses were injected into rats. For statistical analysis of the data, analysis of variance was used and multiple comparisons were determined by Tukey's test. Administration of serotonin HCl MF (5 mT)-exposed rats produced a significant increase in percent maximal possible effect (% MPE) as compared with EMF group (P < 0.05). On the contrary, injection of WAY 100635 to MF-exposed rats produced a significant decrease in analgesic activity (P < 0.05). Similarly, the administration of DOI hydrochloride significantly increased % MPE values as compared with the EMF group while SB 204741 reduced it (P < 0.05). In conclusion, our results suggested that serotonin 5-HT1 and 5-HT2 receptors play an important role in EMF-induced analgesia; however, further research studies are necessary to understand the mechanism. Bioelectromagnetics. 2019;40:319-330. © 2019 Bioelectromagnetics Society.

Coenzyme Q10 increases absence seizures in WAG/Rij rats: The role of the nitric oxide pathway.

Several results have suggested that coenzyme Q10 has protective effects in different models of epilepsy. This study was designed to investigate the acute effect of coenzyme Q10 in genetic absence epileptic WAG/Rij rats. We also determined the role of l-arginine (l-Arg), a biological precursor of nitric oxide (NO), and 7-nitroindazole (7-NI), an inhibitor of neuronal NO synthase (nNOS), on the effects of coenzyme Q10. Electrocorticography (ECoG) recordings were obtained during the 180 min after the administration of the different doses of coenzyme Q10 (25, 50, 100 and 200 mg/kg), l-Arg (500 and 1000 mg/kg), 7-NI (25 and 50 mg/kg) or the combinations of coenzyme Q10 (100 mg/kg) with l-Arg (1000 mg/kg) or 7-NI (50 mg/kg). The total number of spike wave discharges (SWDs) and the mean duration of SWDs were calculated and compared. Coenzyme Q10, at the doses of 50 mg/kg, increased the total number of SWDs but did not changed the mean duration of SWDs. Coenzyme Q10 (100 and 200 mg/kg) or l-Arg (500 and 1000 mg/kg) increased both the total number and the mean duration of SWDs. In contrast, the administration of 7-NI (25 and 50 mg/kg) decreased the total number of SWDs and the mean duration of SWDs. Coadministration of l-Arg enhanced the effect of coenzyme Q10 on the total number of SWDs but not on the mean duration of SWDs. Moreover, the coadministration of 7-NI abolished the effect of coenzyme Q10 on both SWD parameters. The electrophysiological evidences from this study suggest that administration of coenzyme Q10 increases absence seizures by stimulating the synthesis of neuronal NO.

Effect of the allopregnanolone and allotetrahydrodeoxycorticosteron on spike-wave discharges in the EEG of absence epilepsy rat models.

Absence epilepsy is a generalized nonconvulsive type of epilepsy that is characterized by spike-wave discharges (SWD) with a frequency of 2.5-4 Hz in the EEG. The activation of the GABAergic system in central nervous system suppresses convulsive seizures but exacerbates absence seizures. Endogenous neuroactive steroids such as 3α-hydroxy-5α-pregnan-20-one (3α,5α-THPROG; allopregnanolone) and 3α,21-dihydroxy-5α-pregnan-20-one (3α,5α-THDOC, allotetrahydrodeoxycorticosteron) are GABA-A receptor-positive allosteric modulators. Finasteride which is a 5α-reductase inhibitor can selectively block the synthesis of endogenous steroids. In this study, we compared the effects of endogenous steroids (THPROG and THDOC) on SWD by using finasteride-treated Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats as a model of absence epilepsy. Wistar (WIS-THPROG and WIS-THDOC) and WAG/Rij (WAG-THPROG and WAG-THDOC) rats were divided into 4 groups (n = 8). After stereotactic surgical procedures, all rats were prepared for direct cortical EEG measurement. Following finasteride administration to each group, THPROG was administered to WIS-THPROG and WAG-THPROG groups, and THDOC to WIS-THDOC and WAG-THDOC groups intraperitoneally. While there was no any SWD activity detected in WIS-THPROG and WIS-THDOC groups, a significant increase in SWD count in WAG-THPROG (p = 0.012) and in WAG-THDOC (p = 0.012), and in SWD total duration in WAG-THPROG (p = 0.012) and WAG-THDOC groups (p = 0.011) were observed after steroid injection. No difference between the efficacy of THPROG and THDOC on absence seizures in WAG/Rij rats was observed.

Metacognitive interpersonal therapy in group: a feasibility study.

Patients with personality disorders (PDs) other than borderline, with prominent features of social inhibition and over-regulation of emotions, are in need of specialized treatments. Individuals present with poor metacognition, that is the capacity to understand mental states and use psychological knowledge for the sake of purposeful problem solving; and are guided by maladaptive interpersonal schemas. We developed a short-term group intervention, Metacognitive Interpersonal Therapy in Groups (MIT-G), incorporating psychoeducational and experiential elements, to help these individuals become more aware of their drives when interacting with others; and to help them adopt more flexible behaviors via improvements in metacognition. We present results of an effectiveness study, evaluating whether we could replicate the initial positive results of our first pilot randomized controlled trial. Seventeen young adults outpatients with personality disorders were included in the 16 session program. Effect sizes were calculated for change from baseline to treatment end for the primary outcome, symptoms and functioning (Clinical Outcomes in Routine Evaluation Outcome Measure) and then for one putative mechanism of change - metacognition. Emotional dysregulation and alexithymia were also assessed. Qualitative evaluations of the acceptability and subjective impact of the treatment were also performed. MIT-G was acceptable to participants. There were medium to large magnitude changes from pre- to post- treatment on wellbeing, emotion dysregulation, alexithymia and metacognition. These gains were maintained at follow-up. There was evidence of clinically significant change on key variables. MITG appears acceptable to patients, as evidenced by the absence of drop-out from treatment. In light of the positive outcomes of this study and the expanding evidence base, MIT-G is a candidate for dissemination and investigations in larger trials as a possible effective intervention for PDs characterized by tendencies to overcontrol.