Protective effects of 5-HT1A receptor agonists against emotional changes produced by stress stimuli are related to their neuroendocrine effects.
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1. The effects of the 11beta-hydroxylase inhibitor metyrapone on the protective effects of serotonin (5-hydroxytryptamine; 5-HT)(1A) receptor agonists against emotional changes produced by acute restraint stress were examined in mice. 2. Changes in the emotional state of mice were evaluated in terms of changes in exploratory activity, i.e. total locomotor activity, number and duration of rearing and head-dipping behaviours, and latency to the first head-dipping, using an automatic hole-board apparatus. 3. Treatment with the 5-HT(1A) receptor agonists flesinoxan (1 mg kg(-1), i.p.) and R(+)-2-di-n-propylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT; 1 mg kg(-1), i.p.) 24 h prior to exposure to stress significantly suppressed the decrease in various exploratory behaviours that was observed immediately after the exposure to acute restraint stress (60 min). The effects of flesinoxan (1 mg kg(-1), i.p.) and 8-OH-DPAT (1 mg kg(-1), i.p.) were antagonized by co-injection with N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY100635; 1 mg kg(-1), i.p.), a selective 5-HT(1A) receptor antagonist. 4. Flesinoxan (1 mg kg(-1), i.p.) and 8-OH-DPAT (1 mg kg(-1) i.p.) significantly increased the plasma corticosterone level, and these effects of 5-HT(1A) receptor agonists were dose-dependently blocked by pretreatment with metyrapone (12.5 and 25 mg kg(-1), s.c.). 5. Metyrapone (25 mg kg(-1), s.c.) alone did not modify the stress-induced changes in exploratory behaviours. Pretreatment with metyrapone (12.5 and 25 mg kg(-1), s.c.) partly antagonized the protective effects of flesinoxan (1 mg kg(-1), i.p.) and 8-OH-DPAT (1 mg kg(-1), i.p.) with regard to only the number and duration of head-dipping behaviours. 6. These results suggest that activation of the adrenocortical system via 5-HT(1A) receptors may facilitate some adaptive mechanism(s) involved in the recognition of and/or ability to cope with stressful situations. (+info)
Effects of riboflavin repletion during different developmental phases on behavioral patterns, brain nucleic acid and protein contents, and erythrocyte glutathione reductase activity of male rats.
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Effects of riboflavin repletion of rats at various stages of development were evaluated by biochemical and behavioral parameters. One group of dams received diets containing a suboptimal level of riboflavin, approximately 15 mug, and another group, control, received approximately 40 mug of the vitamin daily 2 weeks before mating. Rats fed the control diet received approximately 120 mug riboflavin daily during pregnancy and lactation; suboptimals received approximately 15 mug daily. Some rats fed the control diet were pair-fed to rats fed the suboptimal ration. A group of dams fed the suboptimal diet was switched to control after parturition. At weaning, male offspring were fed the same riboflavin levels their respective dams received before mating except one group, whose dams were fed the suboptimal diet, received the control diet. Male progeny of dams pair-fed the control diet to suboptimal rats were either pair-fed to offspring of suboptimal dams or to offspring riboflavin-repleted at weaning. Rats that always received the suboptimal diet had significantly higher general activity scores at 60 days of age than the scores of other animals. Brains from rats always fed the suboptimal diet and those receiving riboflavin repletion at weaning had lower, sometimes significantly, DNA, RNA, and protein contents than those from other animals. Riboflavin restriction during gestation and lactation, but not gestation alone, appeared to produce permanent alterations in general activity scores and brain nucleic acid and protein contents of male rat progeny. (+info)
Novelty-seeking behaviour and operant oral ethanol self-administration in Wistar rats.
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The aim of the present study was to investigate the relationship between novelty-seeking behaviour and operant oral ethanol self-administration in Wistar rats. The open field and novel object test was used to assess novelty-seeking. Ethanol self-administration was initiated in an operant procedure where ethanol was introduced in the presence of sucrose. Eighteen out of 32 rats were successfully initiated to lever-press for 8% (v/v) ethanol. None of the parameters assessed in the open field (horizontal activity, rearings) or novel object test (number of contacts with an object, exploration time) differed between the initiated and non-initiated subjects. In addition, correlational analysis revealed that response to novelty did not predict individual differences in ethanol intake in the initiated rats. These results suggest that there is no relationship between novelty-seeking and operant ethanol self-administration in Wistar rats. (+info)
Arousal-related P3a to novel auditory stimuli is abolished by a moderately low alcohol dose.
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Concurrent measures of event-related potentials (ERPs) and skin conductance responses were obtained in an auditory oddball task consisting of rare target, rare non-signal unique novel and frequent standard tones. Twelve right-handed male social drinkers participated in all four cells of the balanced placebo design in which effects of beverage and instructions as to the beverage content (expectancy) were independently manipulated. The beverage contained either juice only, or vodka mixed with juice in the ratio that successfully disguised the taste of alcohol and raised average peak blood-alcohol level to 0.045% (45 mg/dl). ERPs were sensitive to adverse effects of mild inebriation, whereas behavioural measures were not affected. Alcohol ingestion reliably increased N2 amplitude and reduced the late positive complex (LPC). A large, fronto-central P3a (280 ms latency) was recorded to novel sounds in the placebo condition, but only on the trials that also evoked electrodermal-orienting responses. Both novel and target stimuli evoked a posterior P3b (340 ms), which was independent of orienting. Alcohol selectively attenuated the P3a to novel sounds on trials with autonomic arousal. This evidence confirms the previously suggested distinction between the subcomponents of the LPC: P3a may be a central index of orienting to novel, task-irrelevant but potentially significant stimuli and is an important component of the arousal system. P3b does not have a clear relationship with arousal and may embody voluntary cognitive processing of rare task-related stimuli. Overall, these results indicate that alcohol affects multiple brain systems concerned with arousal, attentional processes and cognitive-autonomic integration. (+info)
Temperament and Character Inventory (TCI) personality profile and sub-typing in alcoholic patients: a controlled study.
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Cloninger's Temperament and Character Inventory (TCI) personality profile was used to compare alcohol-dependent patients with non-psychiatric control subjects, and a search made for sub-types of alcoholics with different TCI profiles, using the criteria age of onset of alcohol-related problems, paternal dependence on alcohol and familial antecedents of alcohol dependence. Alcohol-dependent patients (n = 38) were characterized by higher Novelty-Seeking [corresponding to Diagnostic and Statistical Manual of Mental Disorders (4th edition) group B personality type] and lower Self-Directedness than non-psychiatric control subjects (n = 47). Lower Self-Directedness indicates a higher probability of personality disorder in the alcohol-dependent population. Only age of onset of alcohol-related problems delineated the two sub-populations with different TCI profiles: early-onset alcoholics (< or =25 years of age, n = 19), but not late-onset ones (n = 16), in comparison with control subjects, were associated with higher Novelty-Seeking. Both early and late-onset patients scored lower on Self-Directedness than control subjects. Self-Directedness and Cooperation scores were lower in early-onset than in late-onset patients. These results in part support Cloninger's typology, and the TCI data add to evidence concerning a higher probability of personality disorder in alcohol-dependent patients, particularly those with early-onset. (+info)
Specific spatial learning deficits become severe with age in beta -amyloid precursor protein transgenic mice that harbor diffuse beta -amyloid deposits but do not form plaques.
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Memory impairment progressing to dementia is the main clinical symptom of Alzheimer's disease (AD). AD is characterized histologically by the presence of beta-amyloid (Abeta) plaques and neurofibrillary tangles in specific brain regions. Although Abeta derived from the Abeta precursor protein (beta-APP) is believed to play a central etiological role in AD, it is not clear whether soluble and/or fibrillar forms are responsible for the memory deficit. We have generated and previously described mice expressing human wild-type beta-APP(751) isoform in neurons. These transgenic mice recapitulate early histopathological features of AD and form Abeta deposits but no plaques. Here we describe a specific and progressive learning and memory impairment in these animals. In the Morris water maze, a spatial memory task sensitive to hippocampal damage, one pedigree already showed significant differences in acquisition in 3-month-old mice that increased in severity with age and were expressed clearly in 6-month- and 2-year-old animals. The second transgenic pedigree displayed a milder impairment with a later age of onset. Performance deficits significantly decreased during the 6 days of training in young but not in aged transgenic animals. Both pedigrees of the transgenic mice differed from wild-type mice by less expressed increase of escape latencies after the platform position had been changed in the reversal experiment and by failure to prefer the goal quadrant in probe trials. Both pedigrees performed at wild-type level in a number of other tests (open field exploration and passive and active place avoidance). The results suggest that plaque formation is not a necessary condition for the neuronal beta-APP(751) transgene-induced memory impairment, which may be caused by beta-APP overexpression, isoform misexpression, or elevated soluble Abeta. (+info)
Effects of apomorphine, ergocornine and piribedil on audiogenic seizures in DBA/2 mice.
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Audiogenic seizures in DBA/2 mice have been studied after administration of drugs believed to act as dopamine agonists. Apomorphine at 0.4 mg/kg delays all phases of the response, the tonic phase is absent after 2.0 mg/kg; the clonic phase is abolished by 10 mg/kg. Ergocornine (0.5-8.0 mg/kg) produces effects on the latency and occurrence of seizure stages similar to those of apomorphine. Piribedil, ET 495 (4-100 mg/kg) is less potent; even after 100 mg/kg clonic and tonic phases occurred in 50% of the mice. (+info)
Dual effect of central injection of recombinant rat interleukin-4 on lipopolysaccharide-induced sickness behavior in rats.
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Systemic administration of the bacterial endotoxin lipopolysaccharide (LPS) has profound depressive effects on behavior that are mediated by the inducible expression of pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-6 and tumor necrosis factor alpha (TNF), in the brain. To assess the regulatory effects of the anti-inflammatory cytokine IL-4 on LPS-induced sickness behavior, rats injected intra-peritoneally (i.p.) with LPS were administered intracerebroventricularly (i.c.v.) with IL-4. IL-4 (30 and 300 ng) potentiated the behavioral effects of LPS (175 microg/1000 g) when both molecules were co-injected. However, when IL-4 (30 ng) was injected 12 h prior to LPS, it blocked the depressing effects of LPS on social exploration. These results indicate that the regulation of cytokine-induced sickness behavior by IL-4 can be either inhibitory or stimulatory depending on the sequencing of IL-4 and LPS treatments. (+info)