bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of hypnotic effects in the rat: Influence of the sleep‐awake cycle
Authors: Meltzer Leonard T. , Serpa Kevin A. 
Published: January 2005

AbstractThe influence of the sleep‐awake cycle of the rat on the apparent hypnotic effects of two benzodiazepine hypnotics, triazolam (short half‐life) and flurazepam (long half‐life), was assessed. Cortical electroencephalographic recordings from freely moving animals were used to determine whether the rats were awake or asleep. When tested during the dark phase of the light‐dark cycle, when rats sleep approximately 50% of each hour, both agents increased sleep, with flurazepam having a longer duration of action than triazolam. In contrast, when tested during the light phase of the light‐dark cycle, when rats sleep approximately 70–90% of each hour, the sleep‐inducing effects of the two agents could not be distinguished. These data emphasize the importance of baseline levels of sleep in assessing hypnotic‐drug effects.
Simple alternation of components in a multiple fixed‐interval fixed‐ratio schedule of food reinforcement in the rat
Authors: Howard James L. , Pollard Gerald T. 
Published: January 2005

AbstractThree rats pressed a lever on a multiple fixed‐interval 60‐sec (FI) fixed‐ratio 30‐response (FR) schedule of food reinforcement. After 1 year of training in which the FI and FR components were programmed to occur with a probability of 0.5 (random alternation), stimulus control was weak: the response rates early in the FI were high and variable. When FI and FR components were programmed to occur one after the other (simple alternation), stimulus control was strong: the response rates early in the FI were low while the rates late in the FI remained high. Results indicate that simple alternation might facilitate the acquisition of a stable baseline for drug testing.
Alzheimer's “syndrome”: Prognosis of subsets with different etiology and preliminary effects of immunotherapy
Authors: Fudenberg H. Hugh , Singh Vijendra K. 
Published: January 2005

AbstractBased on our current work, we have found aberrations of both cellular immunity and humoral immunity in patients with Alzheimer's disease (AD), suggesting that the bodyapos;s immune system plays an important role in the etiology and/or pathophysiology of at least one subset of AD (we consider AD as a “syndrome”, not a disease). Depending upon the nature of the immune deficits and patientsapos; responsiveness to appropriate immunomodulate therapy, we have thus far differentiated four subsets of AD patients: one subset with defect of a specific T cell (e.g., membrane flexibility) and response to therapy with pyrrolidone compounds; a second subset with autoantibodies to neuron‐axon filament proteins–these patients show clinical improvement after therapy with dialyzable leucocyte extract (DLE) containing transfer factor (TF); a third subset with antibodies to brain antigens (autoimmune) for which therapy is not yet developed; and a fourth subset with none of the abnormalities mentioned above, probably heterogeneous due to one or another biochemical abnormality. We believe that different therapeutic modalities will be necessary for different subsets, much like the situation with other “diseases” such as anemia and diabetes. Our therapeutic results provide additional evidence that AD is a syndrome, not a single disease. Moreover, the clincal improvement demonstrates that the defective function in AD is not due to death of neuronal cells, but rather atrophy or physiologic “suppression.”
Bradykinin‐antagonists: Therapeutic perspectives
Authors: Taylor J. E. , DeFeudis F. V. , Moreau J. P. 
Published: January 2005

AbstractIn vitro and in vivo studies of the actions of various antagonists and agonists of bradykinin (BK) B1 and B2 receptors have been reviewed and analyzed. It seems apparent that certain B2‐antagonists, such as [Thi5,8,D‐Phe7]‐BK and D‐Arg0‐[Hyp3,Thi5,8,D‐Phe7]‐BK will serve as valuable model substances for developing new anti‐inflammatory/analgesic drugs. Further development of B1‐antagonists, based on modifications of the structure of des‐Arg9,[Leu8]‐BK, or combined B1/B2‐antagonists might be useful in controlling disease states involving chronic tissue injury and/or prolonged vasopasm.
Comparison of fixed‐ratio and tandem schedules of reinforcement in discrimination of nicotine in rats
Authors: Stolerman I. P. 
Published: January 2005

AbstractThere have been few comparisons between different schedules of reinforcement for establishing drugs as discriminative stimuli. Fixed‐ratio (FR‐10) and tandem variable‐interval 1‐min FR‐10 schedules have, therefore, been compared directly in a conventional, drug‐saline discrimination paradigm with food reinforcement in rats. The drug used for training was nicotine (0.4 mg/kg s.c., “faded” to 0.1 mg/kg s.c.). The discrimination was acquired rapidly under both schedules, with stimulus control by nicotine being slightly superior under the FR‐10 schedule. In 5‐min extinction tests with nicotine, the FR‐10 schedule gave a clear dose‐response curve with a bar‐selection (quantal) index but with generally poor results when the percentage of drug‐appropriate responding (quantitative index) was calculated. In contrast, the tandem schedule yielded clear dose‐response data with both indices. In tests with (+)‐amphetamine, full generalization was obtained with both FR‐10 and tandem schedules and with both quantitative and quantal indices. Tests for generalization to morphine were negative regardless of the training schedule. The results confirm that orderly data may be obtained with either an FR‐10 or a tandem schedule provided that an appropriate index of discriminative response is employed. The results generally support the validity of current practices, and there will probably not be very marked differences between conclusions depending on which schedule is used.
Compound drug discrimination learning
Authors: Järbe Torbjörn U. C. , Hiltunen Arto J. , Swedberg Michael D. B. 
Published: January 2005

AbstractData are summarized which indicate that drug discriminative stimuli (DDS) and exteroceptive, sensory stimuli interact in a systematic manner. Thus recent work revealed that phenomena such as overshadowing, blocking, and conditional discrimination are operable in drug discrimination learning (DDL) experiments involving exteroceptive cues and DDS. Additionally, in a reversal learning experiment, a contextual change differentially affected rate of reversal learning and subsequent generalization test data.
Individual differences in cocaine discrimination
Authors: Goudie Andrew J. , Leathley Michael , McNally Jayne , West C. R. 
Published: January 2005

AbstractThis study involved an attempt to develop a screening test to select animals that would learn a cocaine drug discrimination (DD) rapidly and an analysis of factors affecting rates of acquisition of cocaine DD. Rats (n = 18) were trained initially in a conditioned taste aversion (C.T.A.) procedure with cocaine (36 mg/kg). Subjects were then trained to discriminate cocaine (5 mg/kg) in an operant procedure, and the cocaine generalization curve was determined. Subjects were then tested for cocaine‐induced hyperthermia. Animals that showed weak C.T.A. showed relatively rapid acquisition of DD (rs = –0.56, P > 0.05, two tailed). Cocaine‐induced hyperthermia did not predict speed of acquisition reliably, nor did cocaine's effects on operant responding. Animals were allocated retrospectively to groups of “rapid” and “slow” discriminators. These groups did not differ in generalization ED50s, in sensitivity to cocaine's effects on operant responding, or in hyperthermic responses to cocaine. Thus speed of DD acquisition was not dependent on individual sensitivity to cocaine. Furthermore, “rapid” and “slow” discriminators probably cannot be dissociated in terms of learning ability, since animals that acquired marked C.T.A. showed slow learning of DD. The C.T.A. data suggest that animals sensitive to dysphoric effects of cocaine are less sensitive to the drug's cueing properties and thus that the cocaine cue at 5 mg/kg may be related to its euphoriant actions. It is possible that C.T.A. procedures can be used to select animals that will learn cocaine DD rapidly.
Discriminative stimulus‐ and schedule‐induced rate effects of ethanol in combination with the proposed ethanol antidote Ro 15‐4513
Authors: Hiltunen Arto J. , Järbe Torbjörn U. C. 
Published: January 2005

AbstractTwo different groups of rats were trained to discriminate, 15 min after the injections, between i.p. administered (1) ethanol (ETOH, 1.2 g/kg) or (2) pentylenetetrazol (PTZ, 15 mg/kg) from a non‐drug condition according to a drug discrimination learning (DDL) procedure. Thereafter, combinations of ETOH and Ro 15‐4513 were evaluated in both groups, as well as in a third group, which was trained according to an FR‐10 bar‐pressing procedure. Results indicated that rats trained to discriminate ETOH from saline generalized combinations of ETOH (0.9 and 1.2 g/kg) and Ro 15‐4513 (3 and 10 mg/kg) to the ETOH stimulus. Rats trained to discriminate PTZ from saline (1) disclosed generalization to the PTZ stimulus with Ro 15‐4513 (10 mg/kg) but not with ETOH 0.3–1 g/kg, (2) generalized the effects of combinations of Ro 15‐4513 (10 mg/kg) and ETOH (0.3–1 g/kg) to the PTZ stimulus, and (3) diazepam (DZP, 3 mg/kg) and Ro 15‐1788 (10 mg/kg) antagonized the PTZ‐like discriminative stimulus effects of Ro 15‐4513 (10 mg/kg). Rats trained to press a bar disclosed increases in the response time after treatments with ETOH (0.9 and 1.2 g/kg) and Ro 15‐4513 (3 and 10 mg/kg) as did the DDL animals. Thus, (1) Ro 15‐4513 did not seem to reverse any of the recorded behaviors induced by ETOH, and (2) both DZP and Ro 15‐1788, however, reversed the generalization of Ro 15‐4513 to the PTZ stimulus.
Does the pentylenetetrazole (PTZ) cue reflect PTZ‐induced kindling or PTZ‐induced anxiogenesis?
Authors: Andrews J. S. , Turski L. , Stephens D. N. 
Published: January 2005

AbstractThe discriminative stimulus induced by a subconvulsive dose of pentylenetetrazole (PTZ) in rats is suggested to be anxiogenic in nature; therefore, antagonism of the discriminative stimulus indicates anxiolytic and not anticonvulsant activity. Repeated administration of subconvulsive doses of PTZ eventually leads to seizures, a process known as kindling. The effects of several anxiolytic and anticonvulsant drugs in antagonizing the discriminative stimulus in rats were compared with the effects of the same substances in preventing seizures in rats treated acutely with a high dose of PTZ or in rats exhibiting kindled seizures following repeated low‐dose PTZ treatment. Irrespective of status as an anxiolytic or an anticonvulsant substance, only compounds that antagonized PTZ‐kindled seizures antagonized the PTZ discriminative stimulus. These results illustrate the difficulty in separating the anxiolytic from the anticonvulsant properties of a substance in this model.
Pentobarbital blocks the pentylenetetrazole‐like effect of withdrawal from chronic diazepam
Authors: Mathis D. A. , Emmett‐Oglesby M. W. 
Published: January 2005

AbstractRats trained to detect the stimulus properties of an anxiogenic drug, pentylenetetrazole (PTZ), substitute preciptated withdrawal from chronic administration of diazepam (DZP) for the PTZ stimulus. The present studies tested pentobarbital (PB), ethanol (ETOH), and clonidine (CL) for their ability to block this withdrawal stimulus. Rats were trained to discriminate PTZ (20 mg/kg) in a two‐lever choice task. Prior to chronic administration of DZP, the benzodiazepine (BDZ) antagonist Ro 15‐1788 (0.64–320 mg/kg) did not substitute for PTZ. PB blocked PTZ in a dose‐related manner, but ETOH and CL did not. Following these tests, rats were given DZP (20 mg/kg, ip) every 8 hr for 10 days. On days 7–10 of this regimen, they were tested for substitution of the PTZ stimulus by Ro 15‐1788 (10 mg/kg) and for blockade of this substitution by PB, ETOH, or CL. Ro 15‐1788 substituted fully for PTZ, and this substitution was blocked by PB but not by ETOH and CL. These data parallel recent reports from human studies that CL is ineffective in treating BDZ withdrawal, and they suggest that discrimination of PTZ may have utility for investigating treatments that will suppress the subjective aspect of BDZ withdrawal.
Naloxone as a stimulus for drug discrimination learning
Authors: Kautz Mary A. , Geter Beth , McBride Sharon A. , Mastropaolo John P. , Riley Anthony L. 
Published: January 2005

AbstractAnimals injected with the opiate antagonist naloxone hydrochloride prior to a saccharin‐LiCl pairing and with its vehicle prior to saccharin alone rapidly acquired drug discrimination, avoiding saccharin following the administration of naloxone and consuming saccharin following its vehicle after only three conditioning trials. Control subjects for which naloxone never signalled a saccharin‐LiCl pairing consumed saccharin following both naloxone and vehicle administration. During dose substitution sessions, animals displayed greater drug‐appropriate responding as the dose of naloxone increased. When a range of doses of naltrexone was given in place of naloxone prior to saccharin access, subjects displayed dose‐dependent naloxone‐appropriate responding. When a range of doses of morphine was substituted for naloxone, subjects displayed vehicle‐appropriate responding at all doses. The fact that naloxone was an effective stimulus at low doses and with minimal training suggests that the conditioned taste aversion procedure is a sensitive index of drug discrimination learning.
Asymmetrical cross‐generalization in drug discrimination with lorazepam and pentobarbital training conditions
Authors: Ator Nancy A. , Griffiths Roland R. 
Published: January 2005

AbstractDepressants have been characterized as showing lower specificity as training drugs than drugs from other pharmacological groups, because drug–lever responding has been occasioned by drugs that are very diverse. In contrast, recent work with lorazepam as a training drug under a food‐maintained drug vs. no‐drug discrimination procedure found unreliable pentobarbital generalization, although pentobarbital‐trained animals showed generalization to lorazepam. Exploration of the limits of this asymmetrical cross‐generalization has included manipulation of species and training doses and studies with a variety of classic and novel sedative‐anxiolytic drugs. To date, comparison of lorazepam to other benzodiazepines used as training drugs suggests that the lorazepam training condition appears to result in a lower probability of generalization to other sedative/anxiolytic drugs than other benzodiazepine training conditions. Review of drug discrimination studies with sedative/anxiolytic drugs suggests that there may be more specificity among the depressants as training drugs than initially appeared to be the case.
Sex differences in luteinizing hormone releasing hormone‐induced conditioned place preference in the rat
Authors: de Beun Rene , Geerts Nora E. , van de Poll Nanne E. , Slangen Jef L. , Vreeburg Jan T. M. 
Published: January 2005

AbstractConditioned place‐preference was measured in male and female Wistar rats after association of 5 μg/kg i.p. injections of LHRH with one side of a spatial preference box. Gonadectomized males and females received silastic implants, containing testosterone (T) and estradiol (E), respectively. During an adaptation session of 60 min, at the start of experimentation, possible basic preference for one or the other (black or white) compartment was established. Alternatingly, on 8 subsequent days, LHRH treatment was paired with one compartment (4 × 30 min), and vehicle treatment (saline), with the distinctive second compartment (4 × 30 min). Animals were injected 15 min before the association sessions, which was sufficient to increase circulating LHRH during the first 10–13 min. Finally, at the preference test (non‐drug condition), animals had access to both compartments (test duration 60 min). Male rats spent significantly more time in the part of the test box associated with LHRH treatment, whereas no preference developed in females. The results indicate that injection of a dose of LHRH that was sufficient to activate the pituitary‐gonadal axis in intact rats (unpublished data) is rewarding for male but not for female rats.
Alpha2 agonists and GABAergic agents reverse isoniazid‐induced convulsions in mice
Authors: Aley K. O. , Kulkarni S. K. 
Published: January 2005

AbstractThe effects of GABAergic agents (GABA, fengabine, baclofen) and alpha2 agonists (clonidine and BHT‐920) on isoniazid (INH)‐induced convulsions in mice were studied. All the GABAergic agents and alpha2 agonists employed in the study provided significant protection against INH‐Induced convulsions and death. The protective effects of alpha2 agonists were sensitive to blockade by yohimbine or idazoxan. When a subeffective dose of alpha2 agonist or GABAergic agent was concomitantly administered with a subeffective dose of diazepam, a potentiation of the anticonvulsant effect of diazepam was observed. Alpha2 agonists through GABAergic mechanism offer protection against INH‐induced seizures in mice.
Single‐Subject design for locomotor activity
Authors: Pollard Gerald T. , Howard James L. 
Published: January 2005

AbstractRats were given daily 1‐hr sessions in photocell cages until baseline locomotion stabilized. d‐Amphetamine 0.5–2.0 mg/kg p.o. significantly increased locomotion. Chlorpromazine 2.5–20 mg/kg p.o. and pentobarbital 5.0–20 mg/kg p.o. significantly decreased locomotion. N = 4 per drug. Results demonstrate the appropriateness of using chronic single subjects to assess the effects of drugs on locomotion. An attempt to generate cumulative dose‐effect curves in rats run once a week was less successful because of intrasubject variability. The method could also be used for multiple drug studies in lesioned or cannulated preparations.
Excitotoxicity and N‐methyl‐D‐Aspartate receptors
Authors: Olney John W. 
Published: January 2005

AbstractA great deal of new information has been generated over the past decade in the excitatory amino acid (EAA) field. Not only have endogenous EAA such as glutamate and aspartate become recognized as the leading neurotransmitter candidates at the majority of excitatory synapses in the mammalian central nervous system, but it is becoming increasingly evident that the well‐established neurotoxic (excitotoxic) properties of these agents may play an important role in the pathophysiology of neurodegenerative diseases. Several EAA receptor subtypes have been identified through which the excitotoxicity of EAA might be expressed. One of these—the N‐methyl‐D‐aspartate (NMDA) receptor—has become a primary focus of attention because of evidence suggesting it may be involved in a wide range of both neurophysiological and pathological processes. Antagonists that powerfully block both the excitatory and neurotoxic actions of EAA agonists at the NMDA receptor or associated ion channel have been identified and are being developed as potential neuroprotective agents for use in the management of neurological disorders. In this article, the potential role of excitotoxic mechanisms in neurodegenerative diseases and the prospects for controlling such disease processes by the application of antiexcitotoxin drugs will be examined.
Excitatory amino acid antagonists: Behavioral and biochemical approaches for the development of new central nervous system therapeutic agents
Authors: Wilmot Carole A. 
Published: January 2005

AbstractA general summary of behavioral and biochemical procedures that have been used for the evaluation of excitatory amino acid (EAA) antagonists, primarily those of the N‐methyl‐D‐aspartate (NMDA) subtype, is presented. The effects of both competitive NMDA receptor antagonists and noncompetitive ion channel blockers are compared. In some tests, a specificity by 2‐amino‐5‐phosphonovaleric acid (AP5), phencyclidine, and MK‐801 for antagonism of NMDA receptors vs. other subtypes of EAA receptors has been demonstrated. Antagonists of the quisqualate or kainate subtypes of EAA receptor have been less well characterized.
Cognitive enhancers prevent the hypoxia‐induced disruption of conditioned avoidance response
Authors: Groóa Dóra , Pálosi Eva , Szporny László 
Published: January 2005

AbstractSix cognitive enhancer compounds, the new class of central nervous system (CNS)‐active drugs (vinpocetine, vincamine, dihydroergotoxine, nicergoline, piracetam, and meclofenoxate) were tested before acquired two‐way active avoidance response of spontaneously hypertensive (SH) rats had been disrupted by lowered environmental oxygen concentration (6% oxygen). Exposure to normobaric hypoxia reduced the number of conditioned avoidance responses (CAR) by 44%; at the same time the spontaneous locomotor activity of the animals (measured by the alteration in the number of intertrial crossings) was not considerably decreased, and latency times of conditioned responses were not lengthened significantly. The compounds tested showed protective effect against hypoxia‐induced performance deficit without stimulating spontaneous activity. Vinpocetine antagonized nearly completely CAR blockade in the 1.25‐5.0 mg/kg p.o. dose range, restoring the ratio of avoidance responses to normal level. Vincamine exerted activity at a dose of 20 mg/kg p.o. Dihydroergotoxine and nicergoline were effective at 10 mg/kg p.o., Piracetam and meclofenoxate showed moderate protective activity at 2,000 and 500 mg/kg p.o., respectively. For comparison, the effect of dopaminergic drugs of a different mechanism of action (amphetamine, apomorphine, bromocriptine, and methylphenidate) was also tested in a similar situation. Only amphetamine (at 1.0 mg/kg i.p.) and low doses of apomorphine (0.1 and 1.0 mg/kg) had a favorable effect against hypoxia‐induced CAR blockade; this effect was accompanied by an increase in locomotor activity. On the basis of these data, the relatively simple behavioral method applied by us, protection of acquired conditioned response against the disruptive effect of hypoxia in SH rats, seems suitable to detect nootropic activity.
Effects of endothelium‐derived constricting factor and calcium antagonists on calcium uptake into aortic vascular smooth muscle cells
Authors: Pang David C. , Sperelakis Nicholas , Highsmith Robert F. 
Published: January 2005

AbstractEdothelial cells in culture secrete a protein termed endothelium‐derived constricting factor (EDCF) that elicits vasoconstriction in isolated arteries. In this study, the effect of EDCF on Ca2+ influx into cultured rat aortic smooth muscle cells and on force development in coronary arteries was evaluated and compared to that elicited by depolarization with K+. In addition, the effects of the Ca2+ antagonists bepridil, verapamil, and nitrendipine on EDCF‐ and K+‐induced changes in smooth muscle Ca2+ uptake and contractile force were also quantified and compared. EDCF, but not conditioned media from control cultures of fibroblasts or pituitary cells, enhanced Ca2+ influx into monolayer cultures of rat aortic smooth muscle cells in a time‐ and dose‐dependent manner. The time course of Ca2+ uptake in response to EDCF was similar to that elicited by K+. EDCF also resulted in a time‐ and dose‐dependent increase in isometric force in isolated deendothelialized rings of porcine coronary artery, which was more resistant to washout than that induced by K+. The increase in both Ca2+ influx and isometric tension induced by EDCF was abolished by heating the EDCF preparation to 80°C for 15 min. Bepridil (10 m̈M), verapamil (1 m̈M), and nitrendipine (1 m̈M) either markedly attenuated or completely blocked both EDCF‐ and K+‐induced increases in Ca2+ uptake and contractile force. The similarity between the effect of the Ca2+ antagonists on K+‐ and EDCF‐induced changes in vascular smooth muscle function suggests that a site of action of EDCF may be directed at the voltage‐sensitives Ca2+ channel.