Evaluation of anxiolytic action of ondansetron in rats during withdrawal from chronic chlordiazepoxide.
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Animals↗
Biomedical subjects
H Lal
Publications and source records attributed to H Lal.
Learning and memory-enhancing effects of Ro 15-4513: a comparison with flumazenil.
Synthetic benzodiazepines produce an anterograde amnesia, which can be reversed by selective benzodiazepine antagonists or inverse agonists. It has therefore been suggested that the memory-enhancing effects of the antagonists are due to antagonism of an endogenous "benzodiazepine-like" endocoid. If the memory-enhancing effects of the benzodiazepine antagonists are determined predominantly by the antagonism of such endogenous benzodiazepine-ligands, then it could be hypothesized that administration of an inverse agonist, which produces effects functionally opposite to those of benzodiazepine agonists, may also mimic the effects of benzodiazepine antagonists but not produce effects greater than those of the pure antagonists. The purpose of the present study was therefore to investigate the memory-enhancing effects of the benzodiazepine inverse agonist, ethyl-8-amido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate (Ro 15-4513) in young HSD:(ICR)BR mice and to compare these effects with those of the benzodiazepine antagonist, flumazenil. Pretraining injections of flumazenil and Ro 15-4513 (2.5 and 10.0 mg/kg) enhanced equally, both the acquisition and the retention of a task for 1 week requiring mice to discriminate the correct arm of a T-maze, to avoid a mild electric shock. Pretreatment with Ro 15-4513 also dose-dependently protected the animals from experimental amnesia, induced by the cholinergic receptor antagonist, scopolamine in a second model of memory, in which mice were required to passively avoid a dark chamber after shock. In contrast, Ro 15-4513, injected prior to daily active avoidance sessions, failed to significantly improve either the acquisition or retention performance.(ABSTRACT TRUNCATED AT 250 WORDS)
Amnesia↗
Serum immunoglobulin E levels in children with chronic tonsillitis.
Serum immunoglobulin E (IgE) levels were estimated by ELISA in 50 children with chronic tonsillitis before and after tonsillectomy. When compared with the control group, mean serum IgE concentration was found to be significantly higher in children with chronic tonsillitis (P less than 0.001). After tonsillectomy the levels returned to normal.
Adolescent↗
Effect of adenosine and inosine on carbon tetrachloride-induced liver damage in rats.
Liver damage induced in rats by carbon tetrachloride (CCL4) was obvious macroscopically as well as microscopically in stained sections. Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (gamma-GT) were also significantly raised. Adenosine and inosine effectively countered the damage when these were given before and during the period during which CCl4 produces the typical damage. The beneficial effect was seen in biochemical as well as pathological studies.
Adenosine↗
Protracted withdrawal: sensitization of the anxiogenic response to cocaine in rats concurrently treated with ethanol.
Rats were trained to respond on one lever following an injection of saline and the alternate lever after the anxiogenic drug pentylenetetrazol (PTZ 20 mg/kg), according to a fixed ratio (FR10) schedule of food reinforcement. The trained animals were then administered dependence-producing regimens of either cocaine (20 mg/kg, [IP], three times daily for 7 days) or ethanol (mixed 4.5% w/v with sweetened liquid diet given for 5 days). Separate groups of trained rats were given either subthreshold regimens of cocaine (20 mg/kg, IP, three times daily for 5 days), ethanol (2.25% w/v of the diet given for 5 days), or both. Additional groups were matched for control groups. After discontinuation of these regimens, rats were administered test injections of either saline or cocaine, and tested for elicitation of the PTZ-stimulus at selected intervals of withdrawal. After a saline injection, maximum elicitation of the PTZ-stimulus was observed 12 hours following chronic treatment with the higher dose of ethanol, and 120 hours following longer treatment with cocaine. During those periods of withdrawal when a saline injection failed to produce a PTZ-like stimulus, a test injection of cocaine (10 mg/kg) elicited the PTZ-stimulus in the ethanol withdrawn rats, although only partially eliciting the PTZ-stimulus in the cocaine withdrawn group. In the pair-fed controls, or rats withdrawn from the smaller dosage of either ethanol or cocaine, the test dose of saline or cocaine did not elicit the PTZ-stimulus; only 30% of rats selected the PTZ-appropriate level at the highest dose of cocaine tested (10 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Alcoholism↗
Nutritional requirements in infancy.
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Humans↗
Detection of Chlamydia trachomatis antigen by enzyme immunoassay in patients with pelvic inflammatory disease.
In 27 out of the 60 women clinically suspected to have pelvic inflammatory disease (PID) studied, the C. trachomatis antigen titre was found to be higher than the cut-off value. Since the presence of C. trachomatis antigen was detected in 45 per cent of women, it is suggested that all the PID patients may be investigated by ELISA to confirm the role of C. trachomatis as the etiological agent.
Adult↗
Serum gamma glutamyl transpeptidase in head and neck cancer.
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Female↗
Modulation of benzodiazepine agonist and inverse-agonist receptor binding by GABA during ethanol withdrawal.
1. The present study examined the capacity of GABA to modulate flunitrazepam and Ro15-4513 binding to putative GABAA receptors. Binding was measured in distinct brain regions both before and during selected periods of withdrawal from ethanol. 2. Rats were fed a nutritionally complete liquid ethanol (4.5% w/v) diet for 4 days and at various times after the last dose of ethanol (0, 12, 24, & 72 hr), rats were sacrificed and extensively washed brain membrane fractions were prepared. 3. Competitive inhibition of 3H-flunitrazepam binding by either flunitrazepam or Ro15-4513 (10(-10)M to 10(-7)M) was performed in the absence and presence of GABA (10(-5)M). In the presence of GABA, the apparent affinity for flunitrazepam was increased approximately 1.7 fold and the apparent affinity for Ro15-4513 was decreased by 1.7 fold. 4. No alteration in the capacity of GABA to modulate flunitrazepam or Ro15-4513 affinity (e.g. GABA-shift) was observed in cortical membrane preparations either 12 or 72 hr following ethanol cessation. 5. Further, no changes in GABA-modulation of flunitrazepam binding was evident 0, 12, 24, or 72 hr after the last ethanol dose in membranes prepared from cortex, hippocampus or cerebellum. 6. Therefore, results from the present study indicate that the capacity of GABA to modulate receptor affinity for benzodiazepine agonists and inverse-agonists in rat cortex, hippocampus or cerebellum is not altered during withdrawal from chronic ethanol.
Animals↗
Plasma prolactin and insulin changes on feeding leucine supplemented diet in rats.
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Animals↗
Tear lysozyme levels in bacterial, fungal and viral corneal ulcers.
Low levels of tear lysozyme were observed in patients with infective corneal ulcers, when compared with controls. Lowest levels were seen in patients with bacterial corneal ulcers. The levels of tear lysozyme showed a corresponding decrease with the increase in Schirmer test values; meaning thereby, that in ocular conditions associated with increased rate of tear flow, the lysozyme content in tears tends to be low.
Adult↗
Effect of vitamin D supplementation in lactating rats on the neonatal growth.
In lactating rats consuming a commercial diet adequate in calcium, phosphorus and vitamin D, the effect of supplementation of 3000 IU and 7,500 IU of vitamin D3 on the lactational performance of the dams and soft tissue and skeletal growth in the pups has been investigated. On 28th day of age, the pups in the supplemented groups were significantly heavier than in the control group. Study of the indices of cellular growth in the liver and gastrocnemius muscle revealed that the increase in the soft tissue weight was due to a significant increase in protein, RNA and DNA contents (cellular hyperplasia) without any change in protein/DNA ratio (cell size). In the tibia, compared to controls, the dry bone weight and ash weight were more in the supplemented groups, but ash weight/dry bone weight ratio was not altered. The improvement in the neonatal growth was most probably due to the greater milk yield observed in the dams in supplemented groups and not due to any anabolic effect in the pups since direct administration of 500 IU or 1,000 IU of vitamin D3 in 10 day old pups did not increase their body weight.
Animals↗
Effects of feeding low protein diet with and without leucine supplementation on protein status of lactating females and their pups.
Female rats were fed low protein diet (10% casein) either as such or supplemented with 3% leucine during pregnancy and lactation. Changes in litter size and the survival rate, growth and protein status of the pups were noted. The milk yield and hepatic and mammary gland protein status of the mothers were also studied. Feeding low protein diet reduced litter size, increased their mortality and resulted in poor growth of the pups. It also resulted in poor hepatic and mammary gland protein status of the mothers, as well as reduced their milk yield. On adding 3% leucine to 10% casein in the diet, the changes observed in the low protein group, did not alter in any manner.
Animals↗
Mianserin in the treatment of ethanol withdrawal in the rat: prevention of behaviors indicative of anxiety.
The present investigation was a pilot study to determine whether a single dose of mianserin, which produces long-term down-regulation of serotonin1C (5-HT1c) and 5-HT2 receptors, would prevent anxiogenic behaviors occurring during ethanol withdrawal as evaluated in the elevated plus maze. Male Long-Evans hooded rats were fed a liquid diet containing 4.5 percent ethanol for 4 days. Mianserin (20 mg/kg, i.p.) was injected on the morning of the third day of ethanol administration, or 48 hrs and 7 days prior to testing. When animals were tested either 12 hrs (acute withdrawal) or 5 days (protracted withdrawal) after the last dose of ethanol, anxiogenic behaviors were observed as a significant reduction in both percentage of open-arm entries and time spent on the open arms. In contrast, these anxiogenic behaviors were prevented by pre-injection with mianserin 48 hrs or 7 days prior to testing. Attenuation of this important symptom of ethanol withdrawal is of particular importance because, in addition to the nonaddicting properties of mianserin relative to current anxiolytics, the beneficial effects appear to be long lasting and can be achieved with a single dose.
Animals↗
Immunoglobulins IgG, IgM and IgA levels in preterm and small for date newborns.
Forty preterm [14 small for gestational age (SGA), 26 average for gestational age (AGA)] and 40 term (10 SGA and 30 AGA) babies were tested for immunoglobulins (Ig), G, M and A levels. IgG levels increased with gestational age from 922.00 +/- 14.00 mg/dl at 34 weeks to 1827.33 +/- 184.09 mg/dl at 40 weeks. Mean immunoglobulins were lower in SGA babies. IgG was 1029.59 +/- 122.80 mg/dl in SGA preterm babies and increased to 1262.00 +/- 200.0 mg/dl in 2 kg babies. IgM and IgA although increased with higher birth weight but rise was not statistically significant. More care to avoid infections in preterm and SGA babies, with lower immunoglobulin levels and less resistance, is recommended.
Birth Weight↗
Neurobehavioral biomarkers of aging: influence of genotype and dietary restriction.
Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes. The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole. Age-related behavioral changes, the products of CNS aging, have content and predictive validity with respect to human functional capacities and may, therefore, represent important "neurobehavioral" markers of functional aging. This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity. Studies conducted in the authors' laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns, and hypothetical and empirical examples of these pitfalls are described and discussed. In spite of those concerns, it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging.
Aging↗
Animal models of drug withdrawal symptoms.
There have been few attempts to model subjective symptoms of drug withdrawal using animals as subjects. Two approaches for developing such models are reviewed. First, using drug discrimination methodology, it may be possible to train animals to detect the effects of withdrawal. This method has two difficulties: 1) the only discriminations trained to date involve precipitated withdrawal, and 2) the stimulus controlling behavior is difficult to specify. Second, withdrawal from many drugs of abuse produces the symptom of anxiety, and it seems likely that animal models of anxiety could be useful for studying drug withdrawal. This hypothesis has been explored most fully using subjects trained to detect the discriminative stimulus properties of the putative anxiogenic drug pentylenetetrazole (PTZ). Withdrawal from benzodiazepines or ethanol substitutes fully for PTZ, and withdrawal from cocaine, morphine, and nicotine substitutes partially for PTZ. Emerging data suggest that other animal models of anxiety may also be useful for detecting drug withdrawal. The final portion of this review examines a behavioral test that is very sensitive for detecting physical signs of withdrawal in animals. In subjects maintained on an operant baseline using food as a reinforcer, withdrawal from a drug of dependence frequently is associated with disruption of that operant behavior. For example, tetrahydrocannabinol and cocaine, drugs that are not traditionally seen as having significant withdrawal signs, produce disruption of operant responding when high-dose administration is terminated, and their readministration reverses this behavioral disruption. Based on the observation that withdrawal is associated with anxiogenic stimuli, we suggest a method to determine if disruption of operant behavior may be related to these stimuli.
Animals↗
The effects of 5-HT1B characterizing agents in the mouse elevated plus-maze.
Although the serotonergic system has been implicated in the modulation of anxiety states, the specific receptor subtypes that mediate these states require clarification. The effects of drugs that act preferentially at 5-HT1B receptors were evaluated on the behavior elicited in the elevated plus-maze, an animal model of anxiety. Variations in the intensity of light affected mouse behavior in the plus-maze; lower light intensity increased the entries to and time spent on the open arm in a manner similar to that seen with stress-attenuating circumstances. Opposite effects were observed in high light-intensity, similar to effects seen under elevated stress conditions. Chlordiazepoxide produced increased entries and time spent on the open arm, whereas pentylenetetrazol (PTZ) produced opposite effects. The preferential 5-HT1B agents TFMPP and mCPP exhibited a profile similar to PTZ. The effects of TFMPP in the plus-maze were reversed by chlordiazepoxide, but not by the benzodiazepine receptor antagonist flumazenil, which suggests that this effect is not directly mediated by benzodiazepine receptors. The decreased entries and time spent on the open arm of the maze following TFMPP or mCPP administration was possibly mediated by an antagonistic action at 5-HT1B receptors, since this effect was reversed by the selective 5-HT1B agonist CGS 12066B. The present study further demonstrates the utility of mouse behavior in the elevated plus-maze as a model for identifying anxio-modulatory substances.
Animals↗