Sex differences and role of gonadal hormones on glutamate level in the nucleus accumbens in morphine tolerant rats: a microdialysis study

Sex differences are observed in the development of tolerance to the antinociceptive effect of opioid drugs such as morphine, but the precise underlying mechanism remains unclear. There are evidences about the interaction between gonadal hormones and neuromodulatory systems including opioidergic and glutamatergic systems. We examined the sex differences and the role of gonadal hormones on the glutamate level in the nucleus accumbens in morphine tolerant rats using in vivo microdialysis. A microdialysis probe was implanted into the left nucleus accumbens core of rats and CSF (cerebrospinal fluid) dialysates were collected. The concentration of glutamate was measured by high-performance liquid chromatography with a fluorescence detector. The results showed that after chronic morphine administration, tolerance to antinociceptive effects of morphine was significantly greater in male rats (P<0.001). Sex differences in tolerance to morphine disappeared with gonadectomy of animals. There was also a significant sex difference in the glutamate level in the nucleus accumbens of morphine tolerant rats (P<0.001), ovariectomy of female rats decreased the glutamate level significantly (P<0.001), while gonadectomy did not change the glutamate level in males significantly. In conclusion, these experiments demonstrate that the excitatory amino acid release in the nucleus accumbens may be modulated by an estrogen-sensitive mechanism and play a role in the morphine analgesia and tolerance.     

A meta-analysis of animal studies on disruption of spatial navigation by prenatal cocaine exposure

Water-maze testing has been used to assess prenatal cocaine (PCOC)-induced deficits in behavioral studies of spatial navigation and memory abilities. Effects of PCOC in acquisition or in probe trials over water-maze testing days were rarely detected. Despite an absence of effects of PCOC when data were collapsed over multiple days, there was a potential difference when examined during the first day of acquisition training, characterized by a PCOC-associated decrease in learning efficiency but not capacity. Here, we review studies of PCOC-related changes in day-1 water-maze acquisition training and examine the relationship between experimental methodologies and PCOC-treatment procedures and the variability in effect size estimates across studies. The results revealed a significant increase in latencies to goal platform on acquisition training day-1 in PCOC-exposed offspring vs. controls (effect size: r=0.44). Significant effects attributable to variations in the PCOC-treatment procedures across studies were also identified. The moderating variable of PCOC "dose" was significant as lower doses of PCOC exposure yielded larger treatment effects. "Duration" of PCOC exposure was not significant, although a trend for greater effects was observed in studies that employed longer daily treatment schedules or schedules administered in later gestational periods. This analysis identified a consistent difference in acquisition training day-1 of water-maze testing in PCOC-exposed offspring indicating a PCOC-induced deficiency in spatial learning. These findings of impaired spatial learning efficiency are of particular interest given clinical scenarios involving acutely impaired spatial memory and related learning in PCOC-exposed children that highlight the potential consequences in classroom learning.     

Weight change and incident metabolic syndrome in Iranian men and women; a 3 year follow-up study

Background  

Although the association of weight gain and developing metabolic syndrome (MetS) has been reported in the Western and Asian populations, data on the gender-stratified effects of weight change (including weight loss) on incident MetS and its components in the Middle East Caucasians is still scarce.     

Adjustable primitive pattern generator: a novel cerebellar model for reaching movements

Cerebellum has been assumed as an array of adjustable pattern generators (APGs). In recent years, electrophysiological researches have suggested the existence of modular structures in spinal cord called motor primitives. In our proposed model, each "adjustable primitive pattern generator" (APPG) module in the cerebellum is consisted of a large number of parallel APGs, the output of each module being the weighted sum of the outputs of these APGs. Each spinal field is tuned by a coefficient, representing a descending supraspinal command, which is modulated by ith APPG correspondingly. According to this model, motor control can be interpreted in terms of the modification of these coefficients. Vector summation of force fields implies that the complex nonlinearities in neuronal behavior are eliminated, causing our model to be simple and linear. The force field vectors, derived from motor primitives, depend on the state of movement and its derivative and the time that causes different repertoire of movement. This is physiologically plausible. Our model agrees with virtual trajectory hypothesis, stating that dynamics are not computed explicitly in central nervous system, but the desired trajectory, is fed into the spinal cord. We think that the dysmetria and the ataxia seen in some cerebellar diseases may be the result of local disruption of some APPGs. Accordingly, determining the exact location of related motor primitives in human spinal cord and stimulating them by functional neurostimulation may provide a good management for these clinical signs. Surely, experimental researches and clinical trials are needed to validate our hypothesis.     

A cybernetic view on wind-up

Wind-up is described traditionally as a frequency dependent increase in the excitability of spinal cord neurons, evoked by electrical stimulation of afferent C-fibers. Different kinds of wind-up have been reported, but wind-up of Abeta fibers in hyperalgesic states has gained little attention. In this paper, we present a cybernetic view on Abeta fiber wind-up and consider the involved molecular mechanisms as feedback and feedforward processes. Furthermore, our previous hypothesis, the sprouting phenomenon, is included in this view. Considering the proposed model, wind-up in hyperalgesic states might leave out in three different ways: (1) blocking the NMDA receptors by increasing extracellular Mg2+, 2) blocking the receptors and channels that contribute to Ca2+ inward current, and 3) blocking the Abeta fibers by local anesthetics. It seems that wind-up may be inhibited more effectively by using these three blocking mechanisms simultaneously, because in this case, the feedback process (main controller), the feedforward process (trigger), and Abeta stimulation (trigger) would be inhibited concurrently. Wind up may aggravate the pain in clinical hyperalgesic situations such as post-surgical states, some neuropathic pains, fibromyalgia syndrome, and post-herpetic neuralgia. Surely, clinical studies are needed to validate the effectiveness of our abovementioned suggestions in relieving such clinical pains.     

The effects of hypervitaminosis A in sheep following intramuscular administrations of vitamin A

Ten ewe lambs (median age 11 months and average weight 29.2 ± 2.5 kg) were used in the present study. They were divided into two groups: test (n = 5) and control (n = 5). Housing and all diets were identical. In the test group vitamin A was injected into the thigh muscle at a daily dose of 5000 IU/kg body weight for 16 days. The average final body weight of sheep in the test group was significantly (P < 0.05) less than the control group.     

The Effect of Tapering Period on Plasma Pro-Inflammatory Cytokine Levels and Performance in Elite Male Cyclists

The aim of this study was to investigate the effect of two different tapering period lengths on the concentration of plasma interleukin- 6 (IL-6), interleukin (IL-1β) and tumor necrosis factor-α (TNF-α) and performance in elite male cyclists. To this end, after completing 8 weeks progressive endurance exercise, twenty four high-level endurance cyclists were randomly assigned to one of two groups: a control group of cyclists (n = 12) continued performing progressive weekly training volume for 3 weeks while a taper group of cyclists (n = 12) proceeded with a 50% reduction in weekly training volume relative to the control group. A simulated 40 min time trial (40TT) performance ride was used as the criterion index of performance before and after the tapering period to evaluate the physiological and performance effects of each protocol. Blood samples were collected immediately post-40TT from all participants at the beginning of week 1, and the end of weeks 4, 8, 9 and 11. IL-1β, IL-6 and TNFα were assayed using a standard commercial ELISA kits (Quantikine; R & D Systems, Minneapolis, MN). The mean time to complete the 40TT in the taper group decreased significantly (p < 0.01) after both 1 and 3 weeks with reduced training volume relative to the control group. There were significant reductions in (p < 0.001) IL-1β, IL-6 and TNFα concentrations in the taper group relative to the control group at the end of the 3 week tapering period, but not at the end of the 1 week tapering period. These results demonstrate that both a 1 and a 3 week taper period will result in improved physical performance in trained cyclists but only a 3 week taper period will result in attenuation of post-exercise pro- inflammatory cytokines when compared to those continuing a more intense training regimen.

Key points

• The excessive endurance exercise-induced elevations in pro-inflammatory cytokines would, in turn, stimulate the release of anti-inflammatory cytokines.
• Elevations in pro-inflammatory cytokines indicate athletes are highly susceptible to infections.
• 1and 3-week taper periods will reduce circulating pro-inflammatory cytokine levels thereby possibly limiting the chances of infection and potentially reducing the effects of these cytokines in inducing fatigue-like symptoms in athletes.

Key words: Endurance training, immune, performance, interleukin-1β, interleukin-6, Tumor necrosis factor α.