bluuebunny/crossref_metadata_2025_split huggingface dataset:
Memory for discriminated escape learning: Pharmacologic enhancement and disruption
Authors: Forster Michael J. , Popper Mark D. , Paul Subir K. , Lal Harbans , Retz Konrad C. 
Published: January 2005

AbstractDiscriminated escape behavior of mice in a T‐maze was evaluated as a model for investigation of drug effects upon memory. All studies involved discriminated escape training trials on which footshock offset occurred following a correct goal‐arm choice. Memory was assessed in retention tests that involved either reversal or relearning of the previously trained goal choice. Analyses of discriminated escape acquisition and training‐retention interval were performed to identify parameters yielding either optimal or poor retention. Parameters yielding poor retention in untreated mice were used in studies involving drugs expected to improve retention. Pretraining treatment of mice with either physostigmine (0.08 mg/kg) or HydergineTM (0.64 mg/kg) yielded improved retention scores when training was minimal (a criterion of two consecutive correct choices) and the retention interval was long (168 hr). The effects of scopolamine (0.64 mg/kg) upon memory were assessed in the context of a short retention interval (24 hr) and more complete training (three consecutive correct choices), parameters yielding optimal retention in saline‐treated mice. Scopolamine yielded poorer 24‐hr retention performance when present during training, retention, or at both times. Overall, the results indicate that the discriminated escape procedures described are potentially useful for detection and analysis of pharmacologic modifications of memory processes.
Diazepam tolerance and withdrawal assessed in an animal model of subjective drug effects
Authors: Emmett‐Oglesby Michael W. , Mathis Dian A. , Lal Harbans 
Published: January 2005

AbstractTolerance to and withdrawal from drugs of dependence involves subjective symptoms and physical signs. Until recently, only physical signs associated with these phenomena could be assessed in animals. Recently, however, drug discrimination methodology has been used to bioassay for the occurrence of subjective events in animals; the work reviewed in this paper describes extensions of this general technique to test for subjective aspects of withdrawal from and tolerance to benzodiazepine drugs in rats. The durg dicrimination procedure reinforces differential responding where the controlling stimulus is the presence or absence of a drug‐produced internal stimulus. Although it is impossible to determine the quality (subjective nature) of such stimuli in animals, it is possible to operationally define relationships between classes of stimuli. With regard to the discriminative stimulus produced by pentylenetetrazol (PTZ), data to date show that anxiogenic drugs substitute
for PTZ and anxiolytic drugs block the PTZ stimulus. Because in humans severe anxiety is a frequently seen component of withdrawal from dependence on benzodiazepine drugs, this laboratory initiated experiments to determine if animals trained to detect PTZ and then given chronic treatment with benzodiazepines would substitute a withdrawal state for the
PTZ stimulus. Data reviewed in this paper show that following diazepam administration, treatment with the benzodiazepine antagonist Ro 15‐1788 (RO) produced a dose‐related PTZ‐like stimulus. When given to nondependent animals, RO neither substituted for nor blocked nor enhanced the PTZ stimulus. In additional studies, RO produced a PTZ‐like stimulus when administered once every 3 d in rats maintained chronically on diazepam. Further, rats given a 2‐d regimen of diazepam, 80 mglkgl8 hr, were subsequently tolerant to the PTZ‐blocking action of diazepam. These data demonstrate that the discrimination of PTZ is a useful procedure for assessing subjective aspects of tolerance to and withdrawal from benzodiazepines in animals.
Pharmacological evaluation of HP 370, a potential atypical antipsychotic agent: 2. In vitro profile
Authors: Huger Francis P. , Smith Craig P. , Chiang Yulin , Glamkowski Edward J. , Ellis Daniel B. 
Published: January 2005

AbstractHP 370, 4,9‐dibromo‐6‐(4‐methyl‐1‐piperazinyl)benzo[b]pyrrolo[3,2,1‐jk][1,4] benzodiazepine, a compound that has an atypical antipsychotic profile in vivo, was tested for activity in a number of neurotransmitter receptor binding and uptake assays and compared with serveral typical and atypical antipsychotic compounds. The in vitro profile of HP 370 was most similar to that of clozapine, with the notable exception that HP 370 was inactive as an inhibitor of quinuclidinyl benzilate (QNB) binding (IC50 10−5). HP 370, like clozapine, was a relatively weak and nonselective inhibitor of dopamine (DA) receptor subtypes, whereas sulpiride, another compound reported to be atypical, is a very selective but weak inhibitor of dopamine‐2(D2) receptors. HP 370 and clozapine inhihited WB4101 binding with high affinity, indicating α1‐adrenergic receptor blockade. Neither HP 370 nor the standard neuroleptic compounds inhibited flunitrazepam or gamma‐aminobutyric acid (GABA) binding. HP 370, Clozapine, and sulpiride were inactive as inhibitors of norepinephrine (NE), DA, and 5HT uptake, whereas HP 370 AND clozapine were weark inhibitors of GABA uptake. Based on this in vitro data, the mesolimbic site‐selectivity of HP 370 seen in vivo cannot be explained by anticholinergic GABA‐mimetic activity in the DA‐parative results point to a distinct advantage of an atypical neuroleptic, without the antocholinergic side effects of clozapine.
GABAergic mechanism of interaction of lithium and valproate in discrete rat brain regions following their combind treatment and subsequent withdrawal
Authors: Shukla Girja S. 
Published: January 2005

AbstractRats administered intraperitoneally with 1 mmol lithium carbonate/kg/day, 300 mg valproic acid/kg/day, and their combination for 12 days lithium treatment were found to increase the levels of γ‐aminobutyric acid (GABA) and its synthesizing enzymes, glutamic acid decarboxylase (GAD), in corpus striatum and midbrain regions. However, these elevated treatment alone increased GABA and GAD in the cerebral cortex and hippocampus regions. in adition, an increased cerebellar GABA concentration was observed. The combined treatment of lithium and valproic acid enhanced GABA and GAD levels in all brain regions, except for GABA and GAD in the pons‐medulla. A statistically significant synergistic effect of the two drugs was noticed in elevating GABA and GAD levels in the corpus striatum, cerebral cortex, and midbrain region. Furthermore, the elevated levels remained stable even 2 days after cessation of the combined therapy. The observed stable and synergistic increase in the regional GABA and GAD suggested a possible role of facilitated GABAergic transmission in the mechanism of therapeutic action of lithium and valproic acid combination in the treatment of mania.
Withdrawal from ingested diazepam produces a pentylenetetrazol‐like stimulus in rats
Authors: Harris Cynthia M. , Idemudia Smart O. , Benjamin Daniel , Bhadra Samiran , Lal Harbans 
Published: January 2005

AbstractAn interoceptive stimulus produced by withdrawal from chronic diazepam is similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). Because the PTZ stimulus can be measured objectively in animals, its use was proposed as a bioassay for diazepam‐withdrawal stimuli. In previous studies, diazepam was given chronically by the intraperitoneal route. The purpose of the present study was to determine whether withdrawal from diazepam given in the diet would similarly produce a PTZ‐like subjective effect. Administering drug through the diet has the advantage that it eliminates the necessity of giving injections every 6–8 hr and more closely parallels human chronic dosing. Rats were trained with food‐reward in a two‐lever operant task. Presses on one lever were reinforced after injections of PTZ, 20 mg/kg, and on the other lever after saline. After rats had acquired the PTZ discrimination, training was halted, and they were given diazepam, 240 mg/kg/day, in a nutritionally complete liquid diet. Withdrawal was precipitated after 3 or 4 days of chronic diazepam with the benzodiazepine receptor blocker Ro 15–1788, either after a bolus dose of diazepam, given intraperitoneally, or during continued dietary diazepam. During precipitated withdrawal, the rats selected the PTZ lever, indicating the presence of a PTZ‐like stimulus, and this stimulus was blocked by phenobarbital, 80 mg/kg. The percentage of rats selecting the PTZ lever depended on the dose of Ro 15–1788. By 3.5 days after cessation of chronic diazepam, Ro 15–1788 no longer produced a PTZ‐like stimulus and by 11 days, rats recovered baseline discrimination performance, as indicated by saline‐lever selection after saline injections and PTZ‐lever selection after PTZ. These data indicate that a subjective effect of withdrawal similar to that obtained after parenteral diazepam can be produced after chronic diazepam given daily in the diet.
Behavioral pharmacology of the gamma carboline Wy 47,384: A potential antipsychotic agent
Authors: Moyer John A. , Abou‐Gharbia Magid , Muth Eric A. 
Published: January 2005

AbstractWy 47,384 was examined in an extensive series of in vivo preclinical behavioral tests to determine its possible efficacy and side effect liability as a novel antipsychotic agent. Wy 47,384 was found to suppress avoidance responding following both i.p. and p.o. administration at doses that did not generally impair escape performance. Wy 47,384 also was found to be considerably more potent in antagonizing climbing behavior than stereotyped behavior produced by apomorphine. However, this compound demonstrated some cataleptogenic potential in catalepsy and global behavioral assessment tests. Wy 47,384 also produced limited sedation in motor activity, conflict, and rotorod ataxia tests, but the compound did not interact with ethanol. Wy 47,384 did not demonstrate preclinical anxiolytic activity in conflict behavior tests, and it did not show antidepressant effects in tests designed to assess beta‐adrenergic sensitivity. These studies show that Wy 47,384 is a specific putative antipsychotic agent with limited extrapyramidal and sedative side effect potential.
Suppressive action of propentofylline on coupled and uncoupled glucose oxidations in brain synaptosomes
Authors: Andjus R. K. , Ćirković T. , Marjanović M. , Stefanovich V. 
Published: January 2005

AbstractIn view of a possible beneficial action of some of the xanthine derivatives in brain ischemia or anoxia, metabolic effects of synthetic propentofylline (3‐methyl‐[5′ oxohexyl]‐7‐propyl‐xanthine) have been studied in multiple‐dose experiments with suspensions of rat brain synaptosomes incubated at various temperatures. The rate of D‐[14C] glucose conversion to 14CO2 was measured in the absence or in the presence of 2,4‐dinitrophenol (DNP) used to uncouple oxidative phosphorylations and thus simulate mitochondrial uncoupling accompanying neuronal damage in brain ischemia. Propentofylline suppressed synaptosomal glucose oxidations in a dose‐dependent logit‐linear manner. At 15°C, ED50 concentrations (responsible for the suppression of initial oxidation rates by one half) were highest (8 × 10−3 M) in the case of low‐rate oxidations in Na‐free media and were lowest (7.4 × 10−4 M) in respect to the high‐rate DNP‐stimulated metabolism, which thus appeared as particularly susceptible to propentofylline. Cold‐induced modifications of the metabolic responsiveness of snaptosomes to DNP (flattening of the biphasic DNP log dose‐response profile at reduced incubation temperatures) were intensified by propentofylline, suggesting a synergism between hypothermia and the depressant action of the drug. At equal concentrations, propentofylline strongly inhibited uncoupled oxidations while theophylline remained ineffective or induced even additional stimulatory effects. This is similar to the differential in vivo effects of the two xanthines on brain metabolism and blood flow coupling and further supports the possibility of a protective energy‐sparing role of propentofylline in brain ischemia, particularly effective in association with hypothermia.
Teratological effects of industrial solvents
Authors: Pradhan Sikta , Ghosh Tushar K. , Pradhan Sachin N. 
Published: January 2005

AbstractIncreasing exposure of pregnant mothers to various industrial solvents due to voluntary abuse or involuntary exposure in the work place is raising the possibility of production of teratological effects in the offsprings. Ethanol, which can be broadly categorized as a solvent and which is also extensively abused, is well known for its teratological deragements in humans, termed as “fetal alcohol syndrome” as well as in animals. Benzene and its derivatives (xylene and toluene), alcohols, glycols and glycol ethers, and other solvents have also been reported to produce various types of teratogenic effects in animal (e.g., mice, rats, and rabbits) studies. In the case of toluene, some teratogenic anomalies have been reported in three children of mothers exposed to pure toluene vapor throughout the pregnancy.
Further characterization of 5‐hydroxytryptamine1‐like receptors mediating tachycardia in the cat: No apparent relationship to known subtypes of the 5‐hydroxytryptamine1 binding site
Authors: Saxena Pramod R. 
Published: January 2005

Abstract5‐Hydroxytryptamine (5‐HT) increases heart rate in the spinal‐transected cat by acting on 5‐HT1‐like receptors, since this effect is not modified by ketanserin or MDL 72222 but is blocked by methysergide [Saxena et al., 1985]. These 5‐HT1‐like receptors in the cat heart have been further characterized in this investigation using compounds that have high affinities for 5‐HT1 binding site subtypes. Like 5‐HT, the putative 5‐HT1‐like receptor agonists 5‐carboxamidotryptamine (5‐CT; nanomolar affinities for 5‐HT1A, 5‐HT1B, and 5‐HT1D subtypes) and N‐(3‐acetylaminophenyl) piperazine (BEA 1654; preferential and nanomolar affinity for 5‐HT1A site) elicited dose‐dependent tachycardia. The doses needed to increase heart rate by 50 beats·min−1 were calculated to be 84 ± 6, 4 ± 1 and 21,720 ± 5,200 nmol·kg−1 for 5‐HT, 5‐CT, and BEA 1654, respectively. 8‐Hydroxy‐2‐(di‐N,N‐n‐propylamino)tetralin (8‐OH DPAT; selective nanomolar affinity for 5‐HT1A site) and 5‐methoxy‐3‐(1,2,3,6‐tetrahydro‐4‐pyridinyl)‐1H‐indole (RU 24969; preferential nanomolar affinity for 5‐HT1B site) had little activity. Among antagonists that have nanomolar affinities for all four (5‐HT1A, 5‐HT1B, 5‐HT1C, and 5‐HT1D) 5‐HT1 binding site subtypes, methiothepin, followed by methysergide, showed potent activity against tachycardia induced by 5‐HT, 5‐CT, and/or BEA 1654; metergoline was poorly effective. Mesulergine, which has highest affinity for 5‐HT1C binding subtype, also showed antagonist activity, but this effect was less than that of methiothepin or methysergide. It was concluded that the functional 5‐HT1‐like receptors mediating cardioacceleration in the cat do not seem to be related to any of the 5‐HT1 binding site subtypes identified so far.
Comparison of L‐ and D‐celiprolol in ganglionic‐blocked dogs
Authors: Jolly S. R. , Van Inwegen R. , Schwab A. , Pruss T. P. , Smith R. D. , Wolf P. S. 
Published: January 2005

AbstractThe present study examined effects of the stereoisomers of celiprolol and further examined cardiostimulatory effects of celiprolol. In the anesthetized, ganglionicblocked dog, both I‐ and d‐celiprolol, 3 mg/kg, i.v., showed cardioselective beta adrenoceptor antagonist activity, although blockade of isoproterenol‐induced increases in heart rate and contractile force with I‐celiprolol was more effective. The two stereoisomers had equivalent cardiostimulatory effects, increasing heart rate by 24 ± 7 and 18 ± 3 beats/min and right ventricular contractile force by 37 ± 11 and 24 ± 11%, respectively (all P < 0.05). After propanolol, 1 mg/kg + 0.3 mg/kg/hr, the cardiostimulatory effect of d‐celiprolol was abolished, whereas that of i‐celiprolol was unchanged. Dose‐response curves for heart rate and contractile force stimulation by d‐ and I‐celiprolol were parallel with I‐celiprolol being approximately 100 times more potent than d‐celiprolol and 3 times more potent than racemic celiprolol. These observations suggested that the physiologic effects of celiprolol may be largely mediated via I‐stereoisomer. In additional experiments cardiostimulatory effects of racemic celiprolol, 30 μg/kg, were inhibited by propranolol. Dose‐response curves for celiprolol alone and in the presence of propranolol were parallel. Beta‐blockade shifted the effects 1.5 log units to the right and affected chronotropic and inotropic activities similarly. Biochemical studies of celiprolol showed no significant inhibition of canine kidney sodium potassium ATPase, or of multiple forms of canine cardiac cyclic nucleotide phosphodiesterase. In conclusion, both I‐ and d‐celiprolol are cardioselective beta‐blocking agents with I‐celiprolol being the more potent stereoisomer. Also, the propranolol insensitive cardiac stimulatory activity of celiprolol may illustrate a complex interaction between beta antagonist with and withous ISA rather than a novel positive inotropic mechanism.
Differential effects of anesthetic agents on regional blood flow and central hemodynamic parameters in rats
Authors: Vasthare Usha S. , Irion Glenn L. , Carlsson Christer , Tuma Ronald F. 
Published: January 2005

AbstractThree commonly used anesthetic agents (pentobarbital, chloralose‐urethane, and inactin) were studied in a rat model. The radiolabeled microsphere technique was used to evaluate rats anesthetized (no reaction to pain stimulus) with the three drugs as compared to awake unanesthetized animals. Of the three anesthetic agents studied, pentobarbital caused the smallest alteration in central hemodynamic parameters. Chloralose‐urethane significantly lowered cardiac output (56%), stroke volume (35%), and minute work (51%). Chloralose‐urethane also significantly increased total peripheral resistance (59%). Inactin at the concentration used in the present study had very little effect on cardiac index, heart rate, stroke volume, and minute work but significantly increased total peripheral resistance and mean arterial pressure. All three anesthetic agents reduced cerebral and skeletal muscle blood flows equally. While pentobarbital and chloralose‐urethane significantly decreased renal blood flow (33%), inactin did not change flow to the kidney. It is concluded that anesthetic agents used in small animal experiments should be chosen carefully so that they do not influence blood flow to the organ being studied.
Baclofen does not block interoceptive discriminative stimulus produced by pentylenetetrazol
Authors: Idemudia Smart O. , Lal Harbans 
Published: January 2005

AbstractBaclofen was compared with diazepam for ability to block the interoceptive discriminative stimulus produced by the anxiogenic drug pentylenetetrazol (PTZ). Male hooded rats of the Long Evans strain were trained in two‐lever operant chambers to respond for food reward. Presses on one lever were reinforced after intraperitoneal injections of PTZ (20 mg/kg), and on the other lever after saline. After rats had acquired the PTZ discrimination, it was shown that pretreatment with baclofen failed to block the interoceptive stimulus produced by PTZ, whereas pretreatment with diazepam was effective. As baclofen is ineffective in a conflict procedure as well as in antagonizing the PTZ stimulus, but produces a diazepamlike interoceptive discriminative stimulus, it is concluded that elicitation of the diazepam stimulus may not be related to diazepam's anxiolytic efficacy and that diazepam discrimination may be an inappropriate model for studying anxiolytic properties of drugs. Furthermore, the difference between baclofen and diazepam with respect to anxiolytic efficacy is suggested to be related to receptor specificity. The binding of diazepam facilitates GABAA receptor activity, whereas the binding of baclofen facilitates BABAB receptors Hence, it is suggested that modulation of GABAA receptors may be critical in diazepam's blockade of the PTZ stimulus.
Possible memory‐enhancing properties of vinpocetine
Authors: Coleston Donna M. , Hindmarch Ian 
Published: January 2005

AbstractCritical flicker fusion threshold, choice reaction time, total reaction time, and Sternbergtype memory tasks of digits/words were measured in twelve volunteers after having received vinpocetine or placebo for two days. A significant improvement was recorded in the short‐term memory test following 40 mg of the drug when compared to placebo.
Hoe 288: Indications on the memory‐enhancing effects of a peptidase inhibitor
Authors: Usinger Patricia , Hock Franz J. , Wiemer Gabriele , Gerhards Hermann J. , Henning Rainer , Urbach Hansjörg 
Published: January 2005

AbstractSeveral neuropeptides have recently been found to be involved in motivational, memory, and learning processes. Therefore, we tested the hypothesis that the peptidase (EC 3.4.15.1) inhibitor Hoe 288 modulated cognitive functions. Hoe 288 exhibited nootropic effects in uphill avoidance in mice (30 mg/kg orally administered [p.o.]). Scopolamineinduced amnesia in mice and rats was antagonized after subchronic administration for two or three days (1–10 mg/kg p.o. or intraperitoneally [i.p.]) in step‐through avoidance and an eight‐arm‐radial maze, respectively. The resulting bell‐shaped dose‐response curves had a maximum effect at 3 mg/kg. To elucidate the underlying neurochemical effects, ex vivo experiments in rats were performed: acute or repeated administration of Hoe 288 (0.03 – 3 mg/kg i.p.) induced a significant decrease of acetylcholine (ACh) content in certain brain areas that lasted up to 6 hr after treatment. The reduced brain ACh content was most likely due to an enhanced ACh release, as coadministration of the choline uptake inhibitor hemicholinium‐3 (HC‐3) and Hoe 288 potentiated the decrease of ACh induced by HC‐3. Choline acetyltransferase activity in brain increased after acute and subchronic administration of the peptidase inhibitor. Receptor‐mediated effects of ACh were estimated indirectly by its stimulation of guanylate cyclase. Hoe 288 increased cGMP content in a comparable dose range (0.3 – 1 mg/kg i.p.). The converting enzyme inhibitor Hoe 288 was shown to influence acquisition and retention of information in rodents, and the effects on ACh metabolism are in concordance with results obtained with potential nootropics in animal experiments.