bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac sympathectomy with phenol acutely blunts the postsynaptic adrenergic response
Authors: Jones Carl E. , Gwirtz Patricia A. , Dodd‐o Jeffrey M. , Daniels Stephen E. , Randall John R. 
Published: January 2005

AbstractStudies were performed in anesthetized dogs to determine if topical application of phenol to the heart acutely alters postsynaptic function in addition to destroying efferent sympathetic nerves. Left ventricular dP/dt max as well as segment length shortening (%SL) and maximal rate of shortening (dL/dt max) in the circumflex perfusion territory were measured. Responses to left stellate ganglion stimulation (LSS) and intracircumflex injection of norepinephrine (NE, 0.10‐0.50 m̈g) were recorded before and after application of 85% phenol to the atrioventricular junction and to the circumflex artery and its branches (stage 1) as well as to the myocardial surface (stage 2). Responses of dP/dt max, %SL, and dL/dt max to the various dosages of NE were reduced by 40‐64%, 69‐75%, and 44‐61%, respectively, 1 hr after stage 1, indicating that application of phenol to the coronary arteries and arterio‐ventricular junction attenuated the postsynaptic response to adrenergic stimulation. No further changes occurred 1 hr after stage 2. Responses of dP/dt max and dL/dt max to LSS were reduced by 36% and 57%, respectively, after stage 1 and by 75% and 71% after stage 2. Because of high variability, the response of %SL to LSS were not affected by stage 1 or stage 2 application of phenol. In a secondo of 5 dogs, only stage 2 application of phenol was used. The blunting of the LSS response was similar to that seen with stage 1 followed by stage 2, but the NE response was unaffected. These data indicate that application of phenol to the coronary Vessels and to the atrioventricular junction acutely blunts both the postsynaptic response to afferent nerve stimulation, while application of phenol to the myocardial surface blunts only the response to efferent nerve stimulation. Thus, in acute animal studies, application of phenol to the myocardial surface may provide more reliable result on the effects of ventricular denervation.
Pinaverium bromide: A calcium channel blocker acting selectively on the gastrointestinal tract
Authors: Christen Mme Marie‐Odile , Tassignon Jean‐Pierre 
Published: January 2005

AbstractEvidence is reviewed which indicates that pinaverium bromide (PB) relaxes gatrointestinal (GI) structures mainly by specifically inhibiting Ca+2 influx through potential‐dependent channels that exist on the surface membranes of smooth muscle cells. Its in vivo selectivity for the GI tract appears to be due mainly to its pharmacokinetic properties. Because of its low absorption, typical for quarternary ammonium compounds, and its efficient hepato‐biliary excertion, most of the orally‐administered dose of PB remains in the GI tract. Other mechanisms possibly related to its selectivity, and comparisons between the actions of PB and those Ca2+ ‐antagonists, are also disussed. PB is the only Ca2+ ‐antagonist currently registered for treatment of functional intestinal disorders (e.g., irritable bowel syndrome). A major advantage of orally‐administered PB is that it does not elicit adverse systemic (e.g., cardiovasular) side‐effects at doses that effectively relieve GI spasm, pain, and abnormal motility.
Rats can learn simultaneous four‐drug discriminations in four‐lever boxes
Authors: Overton Donald A. , Shen C. Frank , Crawford Lawrence 
Published: January 2005

AbstractRats were required to learn a four‐drug discrimination in compartments containing four levers. The training drugs were phenobarbital 35 mg/kg, nicotine 0.8 mg/kg, fentanyl 0.04 mg/kg, and methylphenidate 5 mg/kg. Responding on a different lever was reinforced with 0.1 ml sweetened water under each drug condition. The experiment tested whether such four‐drug discriminations could be learned, and whether the rate of acquisition and/or asymptotic accuracy of the discriminations would be increased in boxes where each lever was surrounded by a unique sensory environment created by special materials on the floors, walls, and ceiling in the vicinity of the lever (e.g., plastics, wire screens). Four different training compartments were employed. The required discriminations were learned by most rats. The use of unique decorations around each lever decreased the mean number of sessions before the appearance of discriminative control from 90 to 67. It also made asymptotic accuracy significantly higher in some sensory environments than in others. suggesting that animals “preferred” some environments. The training drugs were apparently not equally discriminable at the doses employed, as both sessions to criterion and asymptotic accuracy differed for the various drugs employed.
Recent development in 2‐pyrrolidinone‐containing nootropics
Authors: Gamzu Elkan , Hoover Toni M. , Gracon Stephen I. , Ninteman Monica V. 
Published: January 2005

AbstractThis paper reviews the development of the concept of nootropics‐‐compounds whose activity appears to be specific to enhancement and protection of those functions of plasticity of the central nervous system that we now call cognition. The rest of the review focuses on clinical and preclinical results reported on 2‐pyrrolidinone‐containing noortropics since 1986. Although the clinical efficacy of these compounds remains to be proved definitively, there are some double‐blind trials that demonstrate superiority against placebo. Preclinically, a wide variety of laboratories continue to demonstrate and expand protective effects of nootropics against various insults of the CNS.
Propentofylline increases the survival rate in gerbils after brain ischemia: Influence on serotonin metabolism
Authors: Mrsulja Bogomir B. , Stefanovich Vladimir 
Published: January 2005

AbstractFollowing the bilateral occulusion of common carotid arteries in gerbils for 15 min, the survival rate and serotonin metabolism were evaluated in groups of animals treated over a period 7 days by propentofylline or pentobarbitalor both propentofylline fo pentobarbital. In the non‐treated group as well as in animals treated by pentobarbital only, survival rate was about 29%, and serotonin metabolism was inhibited, both in the cerebral cortex and basal ganglia. Contrary to that, survival rate of animals treated by propentofylline or propentofylline and pentobarbital was about 70% at the 7th day after 15 min of ischemia, and serotonin metabolism was at the normal rate. These results show the superior effect of propentofylline in comparison to pentobarbital on the survival rate and serotonin metabolism after brain ischemia.
Cardioprotective effects of nicorandil on calcium paradox‐induced injury
Authors: Hamaguchi Tomoyuki , Azuma Junichi , Takihara Keiko , Ohta Hideyuki , Harada Hisato , Sperelakis Nicholas , Kishimoto Susumu 
Published: January 2005

AbstractNicorandil, a new antianginal drug, exerts a coronary vasodilation effect by mechanisms different from either nitrates or slow‐channel Ca++ entry blockers. This agent has been demonstrated to increase membrane K+ conductance, elevate cyclic guanosine monophosphate (GMP) content, and depress Ca++ current kinetics in vascular smooth muscle cells. In the myocardium, however, the direct effects of the agent have not been elucidated. We examined whether or not nicorandil could antagonize myocardial injury in the Langendorff‐perfused chick heart induced by the Ca++ paradox. The Ca++ paradox was produced by 15 min of Ca++‐free perfusion, followed by 10 min of Ca++ reperfusion. Nicorandil was added to the perfusing solution only during the Ca++ reperfusion phase. In the Ca++ paradox hearts, the following were observed: (1) depression of myocardial creatine phosphokinase and adenosine triphosphate (ATP) contents; (2) elevations of myocardial H2O, Na+, and Ca++ contents; and (3) ultrastructural derangement, which included contraction bands, interstitial edema, and mitochondrial swelling. Nicorandil treatment significantly attenuated the histological perturbation and part of the biochemical alterations. The present study suggests that nicorandil partially protects the myocardium against the Ca++ paradox‐induced injury.
HP 818: A centrally acting analgesic with neuroleptic properties
Authors: Locke Kenneth W. , Dunn Robert W. , Hubbard John W. , Vanselous Cheri L. , Cornfeldt Michael , Fielding Stuart , Strupczewski Joseph T. 
Published: January 2005

AbstractHP 818 (1‐benzoyl‐6‐fluoro‐3‐(1‐methyl‐4‐piperidinyl)‐1H‐indazole) exhibits the profile of a potent nonnarcotic analgesic with neuroleptic properties. HP 818 blocks the effects of chemical (phenylquinone), pressure (tail clip), and radiant heat (tail flick) painful stimuli in mice (ED50 values of 0.3, 1.2, and 4.1 mg/kg s.c., respectively). This compound displays antinociceptive activity by the subcutaneous, oral, and intravenous routes of administration. It is also effective in the shock titration assay in squirrel monkeys and in a model of surgically induced pain. The rank order of potency of HP 818 and several other standard compounds in these tests for analgesia was Innovar > fentanyl > HP 818 > codeine > droperidol. In addition to its antinociceptive effects, HP 818 possesses neuroleptic properties. It is active in the climbing mouse, pole climb avoidance, and intracranial self‐stimulation assays (ED50 values of 1.8, 1.7, and 2.5 mg/kg i.p., respectively). Moreover, HP 818 inhibits amphetamine‐ and apomorphine‐induced stereotypy, indicative of D2‐dopaminergic blocking properties. HP 818, unlike typical neuroleptic agents, does not induce supersensitivity to the effects of apomorphine when administered chronically in mice. In contrast to the clinical standard neuroleptanalgesic Innovar, HP 818 (1.0–3.0 mg/kg i.v.) produces no significant cardiovascular or respiratory changes in the anesthetized dog. Thus, HP 818 is potentially an effective presurgical medication due to its nonnarcotic analgesic activity and sedative neuroleptic effects, along with its lack of limiting cardiorespiratory side effects.
Open fixed dose trial of fluoxetine in the treatment of obsessive compulsive disorder
Authors: Kim Suck Won , Dysken Maurice W. 
Published: January 2005

AbstractTwelve non‐depressed DSM‐III obsessive compulsive disorder (OCD) patients were treated with fluoxetine in a 12 week open fixed dose study. After a 2 week washout period, patients were treated with 20 mg/day of fluoxetine for 1 week. The dosage was then raised to 40 mg/day for the remainder of the study. The Yale‐Brown Obsessive Compulsive Scale (Y‐BOCS) score (mean ± SD) decreased from 25.8 ± 4.5 to 15.4 ± 7.0 (P < 0.01) and the Symptom Check List‐90‐Obsessive Compulsive Subscale (SCL‐90‐OC) score (mean ± SD) also showed a decrease from 2.4 ± 0.8 to 1.3 ± 0.9 (P < 0.005). The results suggest that fluoxetine is effective in non‐depressed OCD patients. Our results also show that a 40 mg/day dosage is effective in contrast to previous studies that used 80 mg/day. Our finding of a significant treatment reduction in the SCL‐90‐OC is also in contrast to a previous OCD study in which the SCL‐58‐OC was not significantly reduced.
Influence of trapidil and trapidil derivatives on the content of cyclic nucleotides in human intima cells cultured from atherosclerotic plaques
Authors: Heinroth‐Hoffmann I. , Krüger J. , Tertov V. V. , Orekhov A. N. , Mest H.‐J. 
Published: January 2005

AbstractTrapidil and some other 5,7‐disubstituted s‐triazolo(1,5‐a) pyrimidine derivatives (TD's: AR 12455, AR 12456, AR 12463, AR 12465), which have been shown to possess inhibitory effects on proliferative activity in cultured cells, influenced the cyclic nucleotide level in human intima cells cultured from atherosclerotic plaques. The intracellular cAMP content was increased by all tested substances in concentrations of 10−4M and 10−5M, respectively. The effects of these substances were similar to those of the phosphodiesterase inhibitor methylisobutylxanthine. A significant decrease of intracellular cGMP level was provoked by trapidil and the TD's AR 12456 and AR 12463. It is discussed that trapidil and TD's have antiatherosclerotic properties mediated by changes of the intracellular cyclic nucleotide content.
Inhibition of guinea pig aortic sarcolemmal Ca2+‐Mg2+ ATPase and cAMP phosphodiesterase activity by milrinone
Authors: O'Connor Bernard , Silver Paul J. 
Published: January 2005

AbstractMilrinone is a positive inotrope/vasodilator that inhibits cardiovascular low Km cAMP phosphodiesterase (PDE) and not Na+−K+ ATPase activity. To explore other possible mechanisms of action, we quantitated the effects of milrinone on Ca2+‐stimulated Mg2+ ATPase activity in guinea pig aortic smooth muscle plasma membranes. Milrinone inhibited Ca2+‐ stimulated activity, but not basal activity, in aortic microsomes. Maximum inhibition (70%) occurred at 1 μM, which coincided with the inflection of a parabolic dose‐response curve. In a sarcolemmal‐enriched (F1) aortic preparation, 1 μM cAMP, 1 μM Cl‐930 (another low Km cAMP PDE inhibitor), and 100 μM W‐7 (a calmodulin antagonist) all inhibited Ca2 ‐stimulated Mg2+ ATPase activity. This F1 preparation contained cAMP PDE activity which was inhibited by 1 μM milrinone (26%) and 1 μM Cl‐930 (40%) but not by 100 μM W‐7. The inhibition of F1 Ca2+ ‐Mg2+ ATPase activity by 1 μM milrinone could be diminished by increasing the concentration of CaCl2 in reaction mixtures. In sum, these studies show that milrinone can inhibit vascular sarcolemmal Ca2+ ‐stimulated Mg2+ ATPase activity. However, inhibition may be direct or direct or may be secondary to cAMP PDE inhibition in vascular sarcolemma, since inhibition also occurs with cAMP and another low‐Km cAMP PDE inhibitor, Cl‐930.
Effects of chlordiazepoxide, buspirone, and serotonin receptor agonists and antagonists on responses of squirrel monkeys maintained under second‐order schedules of intramuscular cocaine injection or food presentation
Authors: Nader Michael A. , Barrett James E. 
Published: January 2005

AbstractLever pressing of squirrel monkeys was maintained under second‐order schedules of either food presentation or cocaine injection. The first response after 3 min produced a 2 sec change in the color of a visual stimulus; the tenth stimulus presentation was followed by either an i.m. injection of cocaine (0.3, 1.0, or 2.0 mg/kg) or the delivery of food. The benzodiazepine chlordiazepoxide (0.3‐5.6 mg/kg) increased responding maintained by food at doses that decreased cocaine‐maintained responding. In contrast, buspirone, a novel nonbenzodiazepine anxiolytic (0.001‐0.03 mg/kg), its analog gepirone (0.003‐0.03 mg/kg), and the N serotonin 1A (5‐HT1A) agonist 8‐hydroxy‐2(di‐n‐propylamino)tetralin (8‐OH‐DPAT; 0.0003‐0.001 mg/kg) increased cocaine‐maintained responding at doses that decreased responding maintained by food. The inverse agonist at benzodiazepine receptors β‐carboline‐3‐carboxylic acid ethyl ester (βCCE) only decreased response rates irrespective of the maintaining event. m‐Chlorophenylpiperazine (mCPP), an agonist at 5‐HT1b receptors, increased responding maintained by food while only decreasing cocaine maitained responding (0.001‐0.03 mg/kg), whereas metergoline (0.1‐0.3 mg/kg), a serotonin antagonist with affinity for both 5‐HT1 and 5‐HT2 receptors, produced large response rate increases in both groups of monkeys. Administration of the 5‐HT2 antagonist ketanserin (0.03‐3.0 mg/kg), the 5‐HT1A compound spiroxatrine (0.0003‐0.03 mg/kg), or the nonselective 5‐HT agonist quipazine (0.003‐1.0 mg/kg) resulted in dose‐dependent response rate decreases in both groups. These results further differentiate buspirone and related compounds from typical anxiolytics and suggest a differential involvement of 5‐HTIA receptors in behaviors maintained by cocaine or food presentation.
Effects of RO 15‐4513 and FG 7142 alone and in combination with ethanol on avoidance in the rat
Authors: Galizio Mark , Biddison Elizabeth S. 
Published: January 2005

AbstractRats were trained on a complex avoidance schedule in which responses on one lever postponed shock and responses on another lever occasionally (variable‐interval 45 sec schedule) produced 2 min periods of timeout from avoidance. As shown in previous experiments, ethanol (1.5 or 2.0 g/kg) produced an increase in timeout responding relative to avoidance lever rates. These effects were attenuated in five of the six rats by 6 mg/kg RO 15‐4513, a dose that did not produce consistent intrinsic effects. In contrast, FG 7142 (10 mg/kg) reliably reversed ethanol effects in only one of the six rats tested. These results support the notion that RO 15‐4513 possesses specific ethanol antagonist properties.
Reconciling differences in drug effects on behavior punished or maintained by response‐produced shock
Authors: Galbicka Gregory 
Published: January 2005

AbstractComparable patterns of behavior maintained by different events are affected similarly by certain drugs and differently by others. The present paper argues that patterns of behavior maintained by response‐produced shock (“shock‐maintained behavior”), although similar in appearance to lever pressing maintained by more conventional positive reinforcers, are generated through differential punishment of long interresponse times; hence, drug effects on this behavior should more closely resemble drug effects on pressing suppressed by punishment. Because the operants suppressed in these procedures are diametrically opposed (long interresponse times vs. pressing), the baseline patterns of behavior will differ (suppressing long interresponse times produces high rates of pressing, punishing pressing produces low rates). Furthermore, any drug‐induced changes in the frequency of the punished operant will result in what appear to be dissimilar drug effects if the rate of only one operant class serves as the dependent variable. That is, drugs that increase the rate of pressing that has been suppressed by punishment should increase long interresponse times similarly suppressed. This results in an overall increase in pressing rate under typical punishment procedures, but a decrease in overall pressing rates (an increase in the rate of punished long interresponse times) under shock‐maintenance procedures. Hence, similar drug effects on these inversely related operants should generate opposite changes in pressing rate under the two sets of procedures. A review of the literature revealed this to hold true in 12 of 15 cases. Drug effects on comparable patterns of pressing maintained by shock or food presentation split more evenly. The literature indicates that, of 21 such, comparisons between pressing maintained under fixed‐interval schedules of food or shock, ten yielded comparable drug effects under both, and 11 yielded dissimilar effects. These results suggest that what appear to be dissimilar drug effects on pressing maintained or suppressed by shock may in fact be similar effects on the inversely related operants differentiated under these procedure.
Second‐order schedules and the analysis of human drug‐seeking behavior
Authors: Goldberg S. R. , Schindler C. W. , Lamb R. J. 
Published: January 2005

AbstractBehavior maintained by drug injections can be enhanced by using simple schedules as components of more complex second‐order schedules. Under second‐order schedules, completion of the component schedule, rather than an individual response, produces the drug injection according to another schedule. Each component schedule terminates with the brief presentation of a stimulus that has been associated with drug injection. Research over the past 30 years using these procedures with monkeys and human subjects has allowed an evaluation of the role of conditioned environmental stimuli in the acquisition, maintenance, extinction, and reinstatement of drug‐‐seeking behavior. These results have provided a cross‐validation of human and animal models of drug abuse which would not have been possible using simple schedules of reinforcement.
Behavioral toxicology of solvents
Authors: Glowa John R. 
Published: January 2005

AbstractVolatile organic solvents exhibit a range of behavioral effects from the insidiously toxic to the beneficial. Solvents impair performance in a concentration‐dependent manner that depends on the unique physicochemical properties of each solvent. The toxic effects of solvents range greatly but, at sufficient concentrations, or after prolonged exposure, neurotoxic effects are often seen. Many solvents are both self‐administered and exhibit noxious properties. Solvents may produce some of their primary behavioral effects by altering γ‐amino‐butyric acid (GABA) function. Further studies related to mechanism may lead to a better understanding of means to protect individuals from the effects of solvent exposure, as well as further our knowledge of solvent abuse. Solvents activate the stress axis and, as such, their neuroendocrine effects deserve further characterization, because chronic exposure may result in altered neuronal activity similar to that associated with chronic stress. Methods have been developed to assess for risk of the effects of exposure to solvents, detailing the lowest levels of solvent expected to produce behavioral impairment. Results from these procedures should be applied to the different end points described.
Evidence for an action of heptaminol hydrochloride (Hept‐a‐mylR) on the central nervous system based on an increase in intracranial self‐stimulation behavior in the mouse
Authors: Durantou F. , Cazala P. , Pourrias B. 
Published: January 2005

AbstractThe effects of intraperitoneal injections of heptaminol hydrochloride (Hept‐a‐mylR) on intracranial self‐stimulation (ICSS) in the lateral hypothalamus (LH) were studied in BALB/c mice. In a first experiment, performed in a lever press box, we observed that ICSS induced by brief (0.2 sec) electrical stimulation was enhanced by heptaminol. However, at the two doses administered (34.6 and 60 mg/kg), increases of the lever‐pressing rate were observed only in animals showing high levels of performance before the treatment. In a second experiment, mice were trained in a shuttle‐box to initiate and terminate a continuous stimulation of the LH. In animals showing a weak approach response before the treatment, heptaminol induced a significant reduction of approach latency but only at the dose of 60 mg/kg. In contrast, animals showing a strong approach response appeared more sensitive to heptaminol since a reduction of approach latency was observed at the two doses administered. No concomitant modification of escape latency was observed. These results suggest (1) that heptaminol modulates activity of certain neuronal mechanisms involved in ICSS regulation and (2) that a relationship exists between the reactivity to heptaminol and the sensitivity of hypothalamic sites to electrical stimulation.
Effects of the steroidal antiandrogen win 49596 on fertility and sex accessory tissue growth in the rat
Authors: Batzold Frederick H. , Winneker Richard C. , Snyder Ben W. , Reel Jerry R. 
Published: January 2005

AbstractDaily administration (20–500 mg/kg) of the steroidal androgen receptor antagonist, Win 49596, to mature male rats for 72 days caused a significant dose‐related inhibition of sex accessory tissue growth that also correlated with Win 49596 blood levels. Cohabitation of treated males with cycling females for up to 7 days after 29 and 65 days of treatment resulted in no significant effects on insemination or pregnancy rates as compared to vehicle‐treated controls. Furthermore, testicular growth was normal and there was no histomorphological evidence for effects on spermatogenesis. The data suggested that the androgen antagonist, Win 49596, selectively inhibited prostatic and seminal vesicle growth without compromising reproductive function. This tissue selectivity is explicable on the basis of the high levels of androgen in testicular fluid as compared to prostatic tissue.