Antinociceptive effects of vitamin B-complex: A behavioral and histochemical study in rats.

B-vitamins have been evaluated as a useful adjuvant therapy to treat pain. In spite of clinical and experimental evidence indicating the analgesic effect of B-vitamins, few studies have investigated their effect on aspects of the inflammatory pain response. In the present study, we investigated the analgesic effect of chronic application of B-complex vitamins (Neurobion) using an inflammatory experimental pain model in rats. Nociceptive behavioral responses were evaluated in male Wistar rats after plantar injection of formalin, comparing the treatment group (TG) with Neurobion pretreatment to the control group (CG) without the pretreatment. In addition, neuronal activity in the central pain pathway was evaluated using c-Fos immunohistochemical reactivity and NADPH-d histochemistry. A highly significant reduction of painful behaviors such as licking and flinching were observed in TG, especially during the secondary phase of the formalin test compared to CG. Results suggest that long-term pre-treatment using Neurobion can have a beneficial effect in reducing the chronic phase of pain. In addition, we observed a downregulation of c-Fos and NADPH-d in dorsal spinal neurons, suggesting that the antinociceptive effect induced by Neurobion could be due to a suppression of nociceptive transmission at the spinal level, particularly in the afferent regions of the dorsal spinal horn, which these neurons utilizing nitric oxide at least as one of their pain neurotransmitters.

Role of sex hormones in the effects of sleep deprivation on methamphetamine reward memory.

Sleep deficiency is known as an important risk factor for relapse to drug abuse, especially for the powerful psychostimulant methamphetamine (METH). On the other hand, both drug addiction and sleep neurobiology are affected by sex hormones. We, therefore, aimed to examine the probable effects of sleep deprivation (SD) on methamphetamine (METH) reward memory in male and female rats. Moreover, we asked if sex hormones influence the effects of SD on METH reward memory. Adult male and female Wistar rats were divided into two main groups, sham and gonadectomized groups. Three weeks later, they were conditioned to receive METH (2 mg/kg, i.p.) in the conditioned place preference. METH reward memory was then reinstated following a 10-day extinction period. SD was induced for 72 h, either before or after extinction, in different groups. In gonadectomized animals, they daily received either subcutaneous administration of estrogen (5 µg/0.1 ml oil) or progesterone (2 mg/0.1 ml oil) or dihydrotestosterone (25 mg/0.1 ml oil) for thirteen days, from post-conditioning day to reinstatement session. We found that SD facilitated relapse to METH reward memory, depending on the time interval between SD and METH reinstatement. Furthermore, we found that estrogen and SD showed synergistic effects to facilitate METH reward memory, whereas testosterone and progesterone revealed inhibitory effects in the controls, but not in the SD, animals. Our findings would seem to suggest that sex hormones should be considered as determinant factors to manage METH abuse and relapse to METH seeking/taking behavior, especially for those with sleep deficiency.

Toward reanimating the laughter-involved large-scale brain networks to alleviate affective symptoms.

INTRODUCTION: The practicality of the idea whether the laughter-involved large-scale brain networks can be stimulated to remediate affective symptoms, namely depression, has remained elusive. METHODS: In this study, 25 healthy individuals were tested through 21-channel quantitative electroencephalography (qEEG) setup upon resting state and while submitted to standardized funny video clips (corated by two behavioral neuroscientists and a verified expert comedian, into neutral and mildly to highly funny). We evaluated the individuals' facial expressions against the valence and intensity of each stimulus through the Nuldos face analysis software. The study also employed an eye-tracking setup to examine fixations, gaze, and saccadic movements upon each task. In addition, changes in polygraphic parameters were monitored upon resting state and exposure to clips using the 4-channel Nexus polygraphy setup. RESULTS: The happy facial expression analysis, as a function of rated funny clips, showed a significant difference against neutral videos (p < 0.001). In terms of the polygraphic changes, heart rate variability and the trapezius muscle surface electromyography measures were significantly higher upon exposure to funny vs. neutral videos (p < 0.5). The average pupil size and fixation drifts were significantly higher and lower, respectively, upon exposure to funny videos (p < 0.01). The qEEG data revealed the highest current source density (CSD) for the alpha frequency band localized in the left frontotemporal network (FTN) upon exposure to funny clips. Additionally, left FTN acquired the highest value for theta coherence z-score, while the beta CSD predominantly fell upon the salience network (SN). CONCLUSIONS: These preliminary data support the notion that left FTN may be targeted as a cortical hub for noninvasive neuromodulation as a single or adjunct therapy in remediating affective disorders in the clinical setting. Further studies are needed to test the hypotheses derived from the present report.

Effective connectivity within the corticothalamic circuit in the neuromyelitis optica patients: A comparative study using resting-state fMRI.

Neuromyelitis Optica, which is known as NMO, is a demyelination syndrome and inflammatory condition of the central nervous system that affects the optic nerves. Since structural imaging approaches cannot adequately describe the brain disorders in patients with NMO, functional magnetic resonance imaging (fMRI) can be used. Resting-state fMRI was performed on 25 healthy subjects and 26 NMO patients. After preprocessing the data, the time series belonging to the regions of the middle frontal gyrus (MFG), inferior frontal gyrus (IFG), precuneus (PRE), thalamus (THA), and middle temporal gyrus (MTG) were extracted as components of the corticothalamic circuit. The obtained time series were statistically analyzed as the input of dynamic causal modeling (DCM) in order to evaluate the effective connectivity within the corticothalamic circuit. The statistical analyses showed that the mean of effective connectivity power was significantly higher in the healthy subjects than in the NMO patients. For the healthy subjects, there was no significant difference in effective connectivity power between the two groups of males and females at the significance level of 0.05. In the NMO patients, there was a significant difference between the effective connectivity levels of the male and female groups only for IFG â†’ MFG, in which it was greater in males than in females. The results of our studies showed that resting-state fMRI could exhibit the difference between healthy and NMO subjects.

Interaction of music and emotional stimuli in modulating working memory in macaque monkeys.

Background music is one of the most frequently encountered contextual factors that affect cognitive and emotional functions in humans. However, it is still unclear whether music induces similar effects in nonhuman primates. Answering this question might bring insight to the long-lasting question regarding the ability of nonhuman primates in perceiving and dissociating music from other nonmusical acoustic information. In the present study, macaque monkeys were trained to perform a working memory task that required matching visual stimuli. These stimuli had different emotional content (neutral, negative, and positive). Monkeys performed the task within different background acoustic conditions (music, same-intensity noise, and silence). We hypothesized that the auditory stimuli might interact with emotional information of visual stimuli and modulate monkeys' performance. Furthermore, if the effects of music and noise on monkeys' behavioral measures differ it would mean that monkeys perceived and processed music differently. We found that, monkeys committed more errors and were slower when they encountered stimuli with negative or positive emotional content. In the presence of music, the influence of emotional stimuli on monkeys' performance significantly differed from those of the neutral stimuli, however, in the presence of noise, the effects of emotional stimuli on monkeys' performance were not distinguishable. The dissociable effects of music and noise on monkeys' performance show that the effects of emotional stimuli were dependent on the background acoustic conditions. Our findings indicate that background music and the same-intensity noise were differentially perceived by monkeys and influenced their cognitive functions.

The effects of oxytocin on primates' working memory depend on the emotional valence of contextual factors.

Current models suggest that neuropeptide oxytocin modulates the salience of emotional/social stimuli and consequently influences perceptual, attentional and learning processes that underlie social behaviour. Therefore, oxytocin has been considered as a potential treatment in managing social and communication deficits in neuropsychological disorders. Recent studies indicate that effects of oxytocin on social and cognitive functions greatly vary and even lead to opposite outcomes. The factors leading to such variabilities in behavioural effects of oxytocin and their underlying mechanisms remain unclear. Here, we examined the effects of exogenously administered (intranasal) oxytocin (48 IU) on cognitive functions of macaque monkeys within a controlled experimental condition in a randomized crossover study. Monkeys performed a working memory task in which they memorized and subsequently matched stimuli with different emotional/social content (positive, negative, and neutral) at different levels of cognitive difficulties (delay period). Monkeys' accuracy was lower at longer delay intervals indicating that higher cognitive demands adversely affected their performance. There was a significant difference in accuracy and response time between the three emotional conditions. The effects of oxytocin on monkeys' performance were dependent on the emotional content of stimuli so that oxytocin enhanced the adverse effects of negative stimuli, however, moderated the effects of positive stimuli. Our findings in monkeys do not support models suggesting a general effect of oxytocin in enhancing salience or heightening of attention to social stimuli and instead suggest that the cognitive effects of oxytocin depend on the emotional valence of contextual factors.