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Biomedical subjects

M Tang

Publications and source records attributed to M Tang.

At least 181 records · Page 10Linked to original sources

Prior schedule exposure reduces the acquisition of schedule-induced polydipsia.

Two groups of rats were given different initial histories before exposing them to daily, 2-hr fixed-interval 1-min (FI 1-min) food-pellet sessions with water freely available. For the initial-history phase (approximately 17 weeks), a Schedule-History Group had no water available during FI 1-min sessions, while a Home-Cage-History Group was maintained at the same body weight (80% of free feeding) in home cages. When water then became available for both groups during FI 1-min sessions, the Schedule-History Group was retarded in their rate of acquisition and final level of schedule-induced polydipsia relative to the Home-Cage-History Group. Substitution of 5% ethanol solution for session water in the final phase produced a like intake level for both groups typical for these inducing conditions. It was concluded that the probability of drinking water in a session situation is reduced by a lengthy history of water unavailability, thereby attenuating the acquisition rate and final level of schedule-induced water overdrinking.

Alcohol Drinking↗

The role of central- and peripheral-type benzodiazepine receptors in anxiolytic-agent augmentation of NaCl solution intake: effects of clonazepam and Ro 5-4864.

Two 1,4 benzodiazepines bind preferentially to the central- and peripheral-type benzodiazepine receptor in the brain, clonazepam and Ro 5-4864, respectively. They were administered to rats to determine if the relation between known anxiolytic action and efficacy in augmenting NaCl solution ingestion in rehydrating rats would remain the case for these prototypic agents. Clonazepam (0.062-32.0 mg/kg, PO) was highly potent and efficacious and increased 1.5% NaCl solution intake in a dose-related fashion. Water intake could also be increased, but to a relatively minor degree. Ro 5-4864 (4-8 mg/kg, IP) did not affect 1.5% NaCl solution ingestion, nor did this dose range suppress the augmenting effect of clonazepam (0.5-2.0 mg/kg, PO) on the solution intake. Since clonazepam does, and Ro 5-4864 does not, possess punishment-attenuation properties in other tests, drug augmentation of NaCl solution ingestion by rehydrating rats continues to correlate well with known anxiolytic action.

Animals↗

What schedule-induced polydipsia can tell us about alcoholism.

An animal model of chronic and excessive voluntary (unforced) alcohol ingestion is presented in which, by drinking, animals produce repeated, substantial elevations in blood ethanol concentration and develop physical dependence. The overindulgence is elective in that ethanol is chosen in preference to certain other fluid-ingestive alternatives. Beside the usual demonstrations of acutely compromised motor performance, tolerance development, cross-tolerance, etc., the model demonstrates that the consequences of even short, but continued, daily drinking episodes results in the disruption of reinforced behavior that occurs later in the day when blood ethanol is absent (impaired general functioning). The conditions which induce the ethanol overindulgence can generate a variety of behavioral excesses which places alcoholism in a context of environmentally determined malfunctions that are subject to therapeutic change by altering situational parameters. Efficacious experiments utilizing therapeutic and preventive strategies are described that may serve as suggestions for corresponding human alcoholism intervention strategies.

Alcohol Drinking↗

Adrenoceptor-mediated changes of excitation and contraction in ventricular heart muscle from guinea-pigs and rabbits.

1. The influence of alpha-adrenoceptor stimulation on mechanical and electrophysiological parameters was investigated in ventricular preparations from guinea-pigs and rabbits. Action potential and force of contraction were measured in papillary muscles and ionic currents were measured in isolated myocytes. 2. The effects of alpha-adrenoceptor stimulation were compared with those of beta-adrenoceptor stimulation. 3. In the guinea-pig the stimulation of alpha-adrenoceptors caused a small increase in the force of contraction (less than 10% of the response to beta-adrenoceptor stimulation) which was not accompanied by any increase of the slow calcium inward current. beta-Adrenoceptor stimulation produced large increases in both force of contraction and slow inward calcium current. The noradrenaline-induced increase in the slow inward calcium current was not affected by phentolamine. 4. In the rabbit, alpha-adrenoceptor stimulation produced large increases in the force of contraction (about two thirds of those seen in response to beta-adrenoceptor stimulation). Whereas beta-adrenoceptor stimulation also produced large increases in both maximal upstroke velocity of slow-response action potentials and slow inward calcium current, there was almost no change of both parameters in response to alpha-adrenoceptor stimulation. 5. We conclude that, first, the contribution of alpha-adrenoceptors to adrenoceptor-mediated changes of force of contraction is minimal in the guinea-pig ventricle, and second, the pronounced changes of force of contraction in the rabbit ventricle in response to alpha-adrenoceptor stimulation are unrelated to changes in the slow inward calcium current.

Action Potentials↗

Midazolam and discriminative motor control: chronic administration, withdrawal and modulation by the antagonist Ro 15-1788.

To evaluate the effects of chronic midazolam (8-chloro-6-(2-fluorophenyl)-1-methyl-4H- imidazo[1,5-a][1,4]benzodiazepine) administration on discriminative motor control, rats were trained to hold a force transducer operated with a paw so that it remained between upper and lower limits of a force band for a continuous 1.5-sec period to deliver each food pellet. Acute doses of midazolam (0.75-3.0 mg/kg s.c.) impaired indices of motor performance as well as session work rate, a measure of sedation. Separate groups received chronic midazolam injections either pressession (Before Group) or postsession (After Group), or presession vehicle (Vehicle Group). The After and Vehicle Groups indicated that neither chronic postsession midazolam, its withdrawal, nor time alone, changed motor performance. The Before Group was affected, and although complete tolerance to work-rate decrements developed rapidly to chronic dosing (3.0 mg/kg), tolerance to motor impairment was incomplete even after 4 months. Presession drug probes with midazolam to the After Group revealed that, although tolerance to work-rate decrement had developed, no tolerance had developed with respect to the capacity for midazolam to impair motor performance. During the chronic phase of midazolam injection to the Before Group, sessions that omitted midazolam, or antagonized it with Ro 15-1788, led to improved motor performance (a drug-purge effect). Precipitated withdrawal was not produced by Ro 15-1788, although simple drug withdrawal did disrupt Before Group motor performance after 4 months of chronic dosing. Ensuing sessions showed a marked improvement in motor performance which returned to the original, prechronic, base-line level.

Animals↗

Simultaneous determination of flurazepam and five metabolites in serum by high-performance liquid chromatography and its application to pharmacokinetic studies in rats.

A reversed-phase high-performance liquid chromatographic method is described which allows the quantification of flurazepam and five of its metabolites with a single, isocratic determination. In addition, it has the advantage of possessing a low detection limit and high precision. A 2 mm I.D. column was used to minimize sample size (50 microliter), increase sensitivity and reduce solvent consumption. The method was used to demonstrate that N-1-desalkylflurazepam, the major metabolite, has a short half-life in the rat in contrast to its prolonged life in humans.

Animals↗

On the mechanism of histamine induced enhancement of the cardiac Ca2+ current.

In guinea pig ventricular myocytes, the effect of histamine on the slow Ca2+ current (ICa) was studied and the following results were obtained: (1) Superfusion of cells with histamine resulted in a dose-dependent enhancement of the amplitude of ICa. The threshold concentration of histamine was 10(-8) M, half maximal increase occurred at 3 X 10(-7) M and maximal enhancement (about 3-4-fold) at 5 X 10(-6) M. (2) The histamine effect was greatly reduced by the H2 antagonist cimetidine (10(-5) M) but only slightly by the H1 antagonist diphenhydramine (10(-5) M). (3) Effects of isoprenaline (ISP) and histamine at maximal effective concentrations on ICa were not additive, suggesting that both agents use the same intracellular pathway. Intracellular infusion of a blocker of the cAMP-dependent protein kinase, Rp-cAMPS (10(-4) M), prevented the histamine effect. (4) The involvement of GTP-dependent transducer proteins was studied by cell dialysis with several GTP derivatives. Intracellular application of the stable GDP-analogue, GDP-beta-S, reduced the histamine effect on ICa, whereas the stable GTP analogue, GTP-gamma-S, mimicked the histamine effect.

Animals↗

Characteristics of reserpine-induced suppression of NaCl solution intake in rats.

Effects of single and repeated administration of reserpine on time-limited drinking of a hypertonic (1.5% w/w) NaCl solution were investigated in rats to assess whether this drug possesses anxiolytic action. Rats adapted to a 23-hr water-deprivation schedule with a free-feeding regimen were allowed a daily 1-hr water rehydration session. In the single-administration experiment, reserpine (0.1, 0.2 and 0.4 mg/kg, IP) was administered to rats at 15 min or 23 hr before a drinking session, where the fluid available was 1.5% NaCl solution. Drug was administered every 7th day. In the repeated-administration experiment, reserpine (0.1 mg/kg/day) was injected daily for 10 days 15 min before each drinking session. The fluid available was water on the first 9 days and NaCl solution on the 10th day. Reserpine suppressed NaCl solution intake when it was singly administered at 15 min before the rehydration, whereas no significant change in the fluid intake occurred when it was administered 23 hr before drinking, even though rats showed ptosis in response to 0.2 and 0.4 mg/kg doses. Tolerance developed to the suppressing effect of repeated administration of reserpine on fluid intake, although ptosis and sedation continued and body weights decreased. Tolerance was almost complete after 11 days. The results suggest that reserpine does not have an anxiolytic effect.

Animals↗