Serdar Demirgören

SEX DIFFERENCE IN UP-REGULATION OF NICOTINIC ACETYLCHOLINE RECEPTORS IN RAT BRAIN

This study tested for sex differences in the effects of chronic nicotine administration and withdrawal on nicotinic acetylcholine receptor binding in brain. Rats received nicotine (0.6 mg/kg, s.c.) or saline once daily for 15 days, and were sacrificed 1 or 20 days after termination of treatment. Saturation studies of nAChR binding were performed using [3H]cytisine as the radioligand in whole brain minus cerebellum taken from animals in the chronic treatment groups and from naive rats. Male but not female rats that received chronic nicotine had higher receptor densities than corresponding control groups; up-regulation of nAChR was not seen 20 days after withdrawal. Furthermore, in groups that showed no up-regulation (controls and rats withdrawn for 20 days), nAChR densities were higher in female rats than males. The findings underscore the importance of sex differences in pharmacological responses as well as in basal neurochemical parameters.

Sexually dimorphic cognitive style in rats emerges after puberty.

In a water maze (WM), rats employ different and sexually dimorphic behavioral strategies to solve a place-learning task, a test of cognitive/propositional ability. Puberty is the last step in brain development and marks an important phase with regard to sexually dimorphic cognitive performance and behavior. The present study assessed possible sex differences in cognitive style before and after puberty in a WM place-learning task. Since nitric oxide (NO) is implicated in spatial learning and hippocampal function, and since brain NO(-)(2) + NO(-)(3) levels (stable metabolites of NO) display region-specific sex differences in rat brain, NO(-)(2) + NO(-)(3) levels were determined after behavioral testing. The sex-related style difference emerged very clearly but only in the adult rats, which suggests that the female behavioral strategy in the WM place-learning task requires the presence of female sex hormones at puberty. Although NO(-)(2) + NO(-)(3) levels were higher in the adult rats and males compared to prepubertal and female rats, respectively, no significant correlations emerged between brain NO and behavior. The fact that the behavioral sexually dimorphic cognitive-style effect observed here and in previous studies appears to emerge only after puberty suggests that awareness of such postpubertal sex differences may also be important in human educational and therapeutic contexts.

Nicotine modulates nitric oxide in rat brain

Nicotine exerts its central actions by regulating cationic fluxes through nicotinic acetylcholine receptors (nAChRs). By this effect, the drug likely also modifies events occurring beyond the nAChR, including the regulation of nitric oxide (NO) synthesis. The present study was undertaken to assess the effects of acute and chronic nicotine administration (0.4 mg/kg, s.c.) on levels of NO(-)(2)+NO(-)(3), stable metabolites of NO, in brain regions of male and female rats. Nicotine increased levels of the metabolites, and therefore presumably of NO, with sex differences in the degree of stimulation, the brain regions affected, and the variance between the effects of acute and chronic administration. Prior inhibition of NO synthase eliminated the effect of nicotine in all regions studied. While nicotine appeared to increase NO indirectly via glutamate receptors in the cortex and hippocampus, this was not true of the corpus striatum, where blocking NMDA-type glutamate receptors with MK-801 had no effect. The findings support the view that NO is likely involved in some of the central effects of nicotine.

Neuromuscular deterioration in the early stage of sepsis in rats

IntroductionCritical illness polyneuropathy (CIP) is a clinical condition frequently seen in patients being treated in critical care units in the final stage of sepsis. The etiopathology of CIP is still unclear, and the onset time of appearance of the electrophysiological findings has not been elucidated. The very little research that has been carried out on this topic is limited to clinical electrophysiological and histopathological studies. In this study, electrophysiological alterations in the early stage of experimentally induced sepsis were investigated in septic rats.MethodsWe conducted a prospective, randomized, controlled experimental study in an animal basic science laboratory with 30 male Sprague-Dawley rats, weighing 200 to 250 g. All of the rats were randomly assigned to one of two groups. In the sepsis group (n = 20), cecal ligation and puncture (CLP) was performed to induce experimental sepsis. In the sham-operated group (n = 10), laparotomy without CLP was performed. Before and 24 hours after CLP and laparotomy, the right sciatic nerve was stimulated from the sciatic notch and compound muscle action potentials (CMAPs) were recorded from the gastrocnemius muscle. Recordings of latency, amplitude, and duration of the CMAP were evaluated.ResultsCMAP durations before and 24 hours after surgery were 0.45 ± 0.05 ms and 0.48 ± 0.05 ms, respectively, in the sham-operated group and 0.46 ± 0.05 ms and 0.55 ± 0.01 ms, respectively, in the sepsis group. Latency measurements in the sham-operated group were 0.078 ± 0.010 ms and 0.080 ± 0.015 ms, respectively, whereas measurements were found to be prolonged in the sepsis group: 0.094 ± 0.015 ms and 0.149 ± 0.054 ms before and 24 hours after surgery, respectively (p < 0.05). CMAP amplitudes in the sham-operated group before and 24 hours after surgery were 8.41 ± 0.79 mV and 8.28 ± 1.92 mV, respectively, whereas in the sepsis group the amplitude measurements decreased to 7.60 ± 1.75 mV and 4.87 ± 3.44 mV, respectively (p < 0.05).ConclusionThe results of the study indicate that electrophysiological alterations appear in the first 24 hours after experimental sepsis and are characterized by an increase in latency and a decrease in CMAP amplitude. The results also suggest that electrophysiological findings seen in patients with CIP might appear before clinical signs of CIP.

Effects of tobacco smoking and gender on interhemispheric cognitive function: performance and confidence measures.

Cognitive function in tasks involving interhemispheric processing of verbal and spatial information was studied in 31 college students in a 22 factorial design with chronic smoking status [smoker (10+cigarettes per day) versus non-smoker (no history of smoking)] and gender as the main between-subject factors. The subjects participated in two sessions on two consecutive days. The same task was repeated within the same session with a 15 min interval: smokers were tested before and after smoking whereas non-smokers rested during the interval. Dependent behavioral variables included those of performance (speed and accuracy) and confidence (low rate of non-responding). The verbal task yielded an expected female advantage, and smoking had the gender-specific effect of increasing both speed and accuracy more clearly in males. In addition, smoking decreased the rate of non-responding (increase confidence) in women, thereby affecting preferred strategies for problem solving by shifting the female pattern towards the male pattern. The spatial task, which probably involved a more perceptual, rather than cognitive, level of functioning, produced no clear effects of smoking and gender, and yielded some laterality effects. The acute within-subject smoking manipulation wherein, among smokers, the first test was preceded by 10 + h of deprivation, whereas the second repeated task was preceded by the smoking of a cigarette (i.e. deprivation followed by partial release) did not affect the behavioral measures. In conclusion, smoking had a gender-specific effect on cognitive function: it improved the performance of males in a verbal task and increased the subjective confidence of females thereby affecting the preferred cognitive strategies for problem solving.

Specific binding of [3H]spermidine to membranes of rat brain

Here we report identification of a specific binding site for [ 3 H]spermidine. The affinity of the site for the radioligand is consistent with a role in recognizing and carrying out some of the intracellular activities of polyamines, which are in high concentration within the cytoplasm

Sexually dimorphic cognitive style, female sex hormones, and cortical nitric oxide.

Recent studies using the water maze (WM) found marked sex differences in behavioral strategy employed in place learning tasks in adult rats. When a change in the platform position is introduced following learning the place of a platform (visible or hidden) in a different position, female rats escape to the newly positioned visible platform faster than males. Nitric oxide (NO) is implicated in place learning, and there are regional sex differences in its stable metabolites, NO(2)(-)+NO(3)(-), in rat brain. Furthermore, NO(2)(-)+NO(3)(-) levels are sensitive to ovariectomy in female rats. The effect of sex hormones on brain development and function is well documented. The present study was undertaken to study the effects of ovariectomy and hormonal manipulations on cognitive performance in a WM task designed to test differences in behavioral strategy in Sprague-Dawley rats (n=48) of both sexes. Some of the females rats were ovariectomised and received either hormone replacement (estrogen or progesterone alone or in combination) or the vehicle. Cortical and hippocampal NO(2)(-)+NO(3)(-) levels were determined after behavioral testing. There were no group differences in cognitive ability or non-cognitive factors such as motivation or swim speed. Males and intact females differed in their cognitive style, but hormonal manipulations in female rats did not affect this relative use of behavioral strategy. There was a correlation between performance on the trial where sex differences were most prominent and NO(2)(-)+NO(3)(-) levels in the cortex. Our results suggest that the activational effects of circulating gonadal hormones do not play a major role in sexually dimorphic cognitive styles.

Learning induces changes in the central cholinergic system of the rat in a sexually dimorphic pattern

The involvement of the central cholinergic system in learning and the possible sexual dimorphism in related brain responses were investigated. Rats were exposed to different environmental conditions and to active avoidance learning. The resulting changes were studied using the following approaches: muscarinic receptor binding (MRB), acetylcholinesterase (AChE) and choline acetyltransferase (CAT) activities. The statistical evaluation of the data reveal that learning induces changes, especially in the postsynaptic component of the central cholinergic system, which shows some sexual dimorphism, and that males and females respond with different levels of increased cholinergic activity to informal and associative learning.

Sexually Dimorphic Effect of an Acute Smoking Manipulation on Skin Resistance But Not on Heart-Rate During a Cognitive Verbal Task

In a two-day, two-session experiment where smokers male and female college-student subjects worked on a cognitive verbal task during either the first or second day, and on a cognitive spatial task on the second or first day, smoking was manipulated as an acute independent variable by requiring 10+ hours of pre-experimental abstention, and providing a cigarette during the 15-minute rest period between the two sessions. Non-smoker female and male subjects underwent the same experiment, and hence served as controls for the effects of this acute-smoking manipulation. Overall adaptation (decreased arousal) to the experiment was manifested in a significant increase in skin resistance level (SRL) in all subjects, but when this adaptation effect was statistically controlled, there was a significant smokers by sex interaction during the verbal task only, such that SRL was increased by the cigarette in males, but decreased in females. In contrast, the same analysis indicated only a marked increase in heart-rate (HR) due to smoking, which was unaffected either by sex or by whether the task was the verbal or the (easier) spatial one. We interpret the SRL results as reflecting a sex difference in the direction of transient psychological arousal, and discuss it in relation to evidence in the literature based on self reports, and to evidence (based on HR in this study and on blood pressure in other studies) on physiological (cardiovascular) arousal.

Effects of Nitric Oxide on Morris Water Maze Performance in Rats: Correlation with cGMP Levels

The relationship between cGMP (guanosine 3′,5′ cyclic monophosphate) and CNS amino acid neurotransmission systems have been known since two decades and glutamate has been shown to increase cGMP levels in mouse striatal slices (Ferandelli JA et al., 1973). Activation of glutamate receptors triggers biochemical events stimulating calcium influx (Wroblewski JT et al., 1985) and cGMP accumulation (Novelli A et al., 1987). NO (nitric oxide) is a novel biological messenger molecule in the CNS which is enzymatically formed from L-Arginine by nitric oxide synthase (NOS), a Ca2+-Calmodulin requiring enzyme; citrulline is the co-product (Garthweite J 1991). Glutamate and N-methyl-D-aspartate (NMDA) receptor activation stimulate arginine-citrulline formation and increase cGMP levels in the cerebellum; L-NG-monomethyl-arginine (L-NMMA) inhibits NOS and prevents the stimulation of cGMP formation (Bredt DS and Snyder SH 1989, Garthweite J et al 1989). NMD A receptor activation has thus been linked to NO.