bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of ethanol on motor activity of the colon in the rat
Authors: Meshkinpour Hooshang , Yu Jen , Harmon David 
Published: January 2005

AbstractThe present study was designed to evaluate the influence of oral and intravenous ethanol on both resting and neostigmine‐induced motor activity of the colon in the rat. Recording assemblies were implanted in the proximal and distal colon in a chronic preparation. On separate days, 2 ml of normal saline or the same volume of 10% or 25% ethanol was introduced intravenously or into the stomach. Colon motor activity was recorded at resting and after intravenous injection of 0.07 mg/kg neostigmine. Ethanol decreased the number and amplitude of the contractions. This effect occurred within a few minutes after administration of ethanol and lasted for the entire recording period of 30 min. Both concentrations of ethanol significantly (P < 0.05) decreased the motility index of the colon. Injection of neostigmine was signified by a substantial rise in colon motor activity which was significantly inhibited by administration of ethanol. These studies indicate that ethanol, within the human legal intoxication range, inhibits the resting and neostimine‐induced motor activity in the rat colon.
Autoimmunity to cholinergic‐specific antigens of the brain in senile dementia of the Alzheimer's type
Authors: Fillit Howard , Foley P. , Bradford H. F. , Bucht G. , Winblad B. , McEwen B. , Luine V. , Hardy J. 
Published: January 2005

AbstractSenile dementia is a common and devastating disease of the elderly. The most common type of senile dementia is Alzheimerapos;s type (SDAT). The cause of SDAT is unknown. Considerable evidence indicates that the basal forebrain cholinergic system of the brain is primarily involved in the disease process. The mechanisms which account for this specificity of injury is unknown. Several lines of evidence have suggested that autoimmunity may play a role in SDAT. In particular, the presence of antibrain antibodies in the sera of patients with SDAT has been described. However, their specificity has not been defined. Our hypothesis proposes that cholinergic‐specific autoimmunity might play a role in the immunopathogenesis of SDAT. We previously presented data to suggest that antibrain antibodies in SDAT sera are directed against cholinergic‐specific brain antigens. In the current study, a synaptosomal lysis assay was employed to determine if SDAT sera caused specific complement‐dependent immunolysis of cholinergic synaptosomes. Immunolysis was determined by the release of choline acetyltransferase (ChAT), glutamate decarboxylase (GAD), dopamine‐beta‐hydroxylase (DBH), lactate dehydrogenase (LDH), and the inhibition of high affinity choline uptake. Sera from two (American and Swedish) groups of SDAT patients and controls were pair‐tested in a blinded fashion on a single batch of synaptosomes. The results demonstrated that both groups of SDAT sera caused significant specific immunolysis of cholinergic synaptosomes. ChAT release, LDH release, and inhibition of choline uptake were caused by SDAT sera in the presence of complement, while control sera showed little effect. No effect was noted on GAD or DBH release. These data support the hypothesis that a cholinergic‐specific autoimmune response may play a role in the immunopathogenesis of SDAT. Further studies are needed to define the immunochemistry of the cholinergic‐specific antigens recognized by SDAT sera.
Immune actions in the nervous system: A brief review with special emphasis on Aalzheimer's disease
Authors: Rogers Joseph , Luber‐Narod Judith 
Published: January 2005

AbstractThe traditional dogma of brain immunologic privilege remains entrenched in the neurosciences. Thus the new discipline of neuroimmunology has often been understood as the study of effects of the nervous system on the immune system rather than vice versa. New data, however, are beginning to show potentially important interactions of the immune system in brain, especially in neurologic disease. These neuroimmune mechanisms appear to involve classic peripheral immune cells (e.g., T cells) as well as cells idiosyncratic to brain (e.g., glia).
Learning and memory deficits associated with autoimmunity: Significance in aging and Alzheimer's disease
Authors: Forster Michael J. , Retz Konrad C. , Lal Harbans 
Published: January 2005

AbstractThis review focuses on the significance of brain‐reactive antibodies (BRA) to ageassociated cognitive decline and Alzheimerapos;s disease, drawing on evidence available from both human and animal studies. Human studies suggest a relationship between BRA formation, age, and Alzheimerapos;s disease. Experiments with mice indicate that BRA formation and age‐related learning deficits are accelerated following adoptive transfer of immunity from aged to young mice. Furthermore, mice selected for autoimmunity and early formation of BRA also show accelerated, age‐related learning deficits. It is concluded that a further analysis of the nature of BRA and their targets within the nervous system could reveal important immunological influences in cognitive dysfunctions related to aging and Alzheimerapos;s disease. It is suggested that treatments that delay or prevent age‐related immunological dysfunctions be evaluated for their ability to retard age‐associated cognitive decline.
Gangliosides in treatment of neural injury and disease
Authors: Mahadik Sahebarao P. , Karpiak Stephen K. 
Published: January 2005

AbstractGangliosides are being used therapeutically to treat a variety of nervous system disorders including peripheral neuropathies and stroke. Gangliosides (over 70 molecular species) are glycosphingolipids found in highest concentration in neural tissue. They are thought to be functional in such diverse biological processes as embryogenesis and cell death, and specifically in membrane‐mediated processes (cell‐cell interactions, ionic balance, synaptic transmission, and receptor‐mediated information transfer). Their distribution changes during neural development, indicative of differential roles for each molecular species at critical stages of development. Ganglioside distribution differs during abnormal development or after neural injury due to trauma or disease. In vivo and in vitro studies have shown that exogenous gangliosides can substitute (structrally and functionally) for the endogenous molecules. This has made it possible to investigate the molecular mechanisms of ganglioside function in situ. During the genesis of these studies it became clear that exogenous gangliosides were able to protect the chemical and morphological changes associated with neural (CNS and PNS) tissue injury (mechanical, ischemic, and neurotoxic). This protective effect has been characterized by facilitated functional recovery in a number of CNS injury paradigms. The mechanism(s) for the facilitative effect of ganglioside treatment is unidentified. Data support a number of hypotheses. One contends that gangliosides can acutely reduce the extent of CNS injury and pathology by protection of membrane structure/function, thereby leading to reduced functional deficits and therefore to increased potential for functional recovery. Another hypothesis supports the view that these glycosphingolipids may promote neuronal regeneration through modulation of trophic factors. Studying the effects of exogenous gangliosides on CNS injury is leading to further insight into the critical functions of endogenous gangliosides as well as focusing attention on the potential of exogenous gangliosides as a therapeutic treatment of traumatic and degenerative CNS disorders.
Drug discrimination procedures: A method to analyze adaptation level of affective states
Authors: Gauvin David V. , Harland Richard D. , Holloway Frank A. 
Published: January 2005

AbstractWhen contrasting drugs (i.e., chlordiazepoxide versus pentylenetetrazol) are examined in drug‐drug, drug‐saline, or drug 1‐drug 2‐saline tasks, one can begin to assess whether such drugs represent orthogonal cues or reflect an underlying cue dimension. Both adaptation level theory and opponent‐process theory are applied to the analysis of drug discriminative performance. Three indices that can differentiate between orthogonal and opponent affective states utilizing drug‐drug discrimination tasks are discussed in relation to these two theories, and a model to characterize further the similarity between pharmacologically and environmentally induced anxiety is proposed.
Stimulant drugs as conditioned and unconditioned stimuli in a classical conditioning paradigm
Authors: Carey Robert J. 
Published: January 2005

AbstractA number of important ways in which drugs interact with learning processes have been identified in studies of the behavioral pharmacology of centrally active drugs. For example, drugs can act as discriminative and as reinforcement stimuli or as unconditioned stimuli eliciting unconditioned responses. Regarding the latter, it has been shown that a number of drug effects can be conditioned to exteroceptive stimuli, providing a mechanism by which drug effects can be transferred from the drug itself to external environment stimulus control. This paper focuses on the development of conditioned drug responses using drug‐induced rotational behavior in rats with unilateral lesions of dopamine neurons. A particularly useful advantage of this model is that the drug‐induced response is mediated by a specific central nervous system (CNS) substrate and the criterion rotational response is unambiguous and easily quantified. Additionally, different drugs can elicit the same response of rotation but in a different direction (i.e., depending on the drug used to induce rotation, ipsilateral or contralateral to the dopamine‐denervated hemisphere). This difference in directionality of drug‐induced rotation provides an opportunity to condition responses to different stimulant drugs differentially, which is not possible in the intact animal, since these drugs tend to evoke similar responses (e.g., hyperactivity or stereotypy). Another advantage of directionality differences in rotational responses associated with different stimulant drugs is that one can assess conditioning interactions between drugs. For example, if one drug that elicits an ipsilateral rotation is paired with another drug that elicits contralateral rotation, then, through a conditioning paradigm of paired drug presentations, one might shift the direction of rotation of the one drug used as the conditioned stimulus to that of the other drug used as the unconditioned stimulus. A number of procedures are described in which the anticholinergic drug scopolamine (which elicits ipsilateral rotation) is paired as the conditioned stimulus with the dopaminergic drug apomorphine (which elicits contralateral rotation) as the unconditioned stimulus, and, as a result, the scopolamine comes to elicit contralateral rotation when subsequently given alone. Observation of such effects points to the importance of drug–drug interactions influenced by Pavlovian conditioning processes.
Voltage‐ and rate‐dependent reduction of Vmax of cardiac action potentials by SC‐40230
Authors: Martin Cynthia L. , Borowicz Luanne E. , Schniepp Henry C. , Sanguinetti Michael C. 
Published: January 2005

AbstractThe voltage‐, rate‐, and concentration‐dependent effects of a new antiarrhythmic agent, SC‐40230, which is chemically similar to disobutamide, on cardiac action potentials were evaluated. Racemic SC‐40230 and its two stereoisomers caused equipotent reduction of the maximum rate of depolarization (V̇max) of action potentials recorded from guinea pig papillary muscle. Action potential duration and effective refractory period were shortened by the drug in papillary muscle and canine Purkinje fibers, but were not altered in guinea pig atria. Depression of V̇max by racemic drug was similar in all three preparations. SC‐40230 did not cause significant reduction of V̇max following a long rest period (no “rested state” reduction). Rate‐dependent depression of V̇max was observed when papillary muscles were stimulated at rates slower, but not greater than 30 pulses/min. In papillary muscles depolarized by 10 mK Ko+, steady‐state depression of V̇max during a stimulus train of 200 pulses/min was 18% in the absence of drug and 56% in the presence of 30 μM SC‐40230. Onset of V̇max reduction was monoexponential (rate constant = 0.064 [action potentials]−1). Recovery from depression of V̇max following the train of stimuli was monoexponential in both control (tau = 11.0 sec) and in the presence of 30 μM SC‐40230 (tau = 27.8 sec). Thus, SC‐40230 appears to slow recovery from slow inactivation of Na current. Rate‐dependent depression of V̇max was voltage dependent. The V1/2 for the relationship between V̇max and resting membrane potential was shifted by −8 mV when determined at a stimulation rate of 120 pulses/min, but was not altered at 12 pulses/min by the drug. Thus, SC‐40230 has typical class I activity on isolated cardiac muscle, but lacks the toxicity of disobutamide.
Effects of sigma agonist and antagonist drugs on food and/or water intake in rats
Authors: Katz Norman L. , Sobaski Nancy , Sanchez Jenny , Kremer Edna K. , Lee Jamie K. , Schlemmer R. Francis 
Published: January 2005

AbstractDrugs known to interact with sigma receptors were studied for their effects on food and/or water intake, since the putative sigma receptor agonist N‐allylnormetazocine (NANM) has been reported to both increase and decrease food intake under various conditions. Previous investigators have shown that each enantiomer of racemic NANM [(±)‐NANM] is pharmacologically active. (+)‐NANM appears to interact preferentially with sigma receptors, and (−)‐NANM with both mu and kappa opiate receptor sites. In the present study, the effects of subcutaneously administered (±)‐NANM, (+)‐NANM, and (−)‐NANM on food intake in 20 hr food‐deprived male rats were examined. (±)‐NANM and (−)‐NANM decreased food intake stimulated by food deprivation, while (+)‐NANM exhibited no significant effect. Similarly, both (±)‐NANM and (−)‐NANM decreased water intake in 24 hr water‐deprived rats. (+)‐NANM decreased water intake in doses which may have caused disorientation. Locomotor activity was stimulated by intraperitoneal injection of 10 mg/kg of (+)‐NANM but not by the same dose of (−)‐NANM. The effects of (+)‐NANM and (−)‐NANM on food and water intake paralleled those of narcotic antagonists and did not seem related to an interaction with sigma receptors. (±)‐BMY14802 is a sigma receptor antagonist with potential antipsychotic properties. When administered to female rats by daily injection for 28 days, it did not affect weight gain except at the highest dose, 30 mg/kg. Weight gain of animals given a 30 mg/kg dose was significantly greater compared to controls. However, rats treated orally with a similar dose of (±)‐BMY14802 incorporated into the diet daily for 8 weeks did not exhibit significant weight gain compared to controls. The data argue against a significant role for sigma receptors in mediating ingestive behavior. Should sigma antagonist drugs reach the market, they may be less likely to cause weight gain than most classical antipsychotics.
Cognition enhancement by the acetylcholine releaser DuP 996
Authors: Cook Leonard , Nickolson Victor J. , Steinfels George F. , Rohrbach Kenneth W. , Denoble Victor J. 
Published: January 2005

AbstractDuP 996, 3,3,‐Bis(4‐pyridinylmethyl)‐1‐phenylindolin‐2‐one, a potent in vitro and in vivo releaser of acetylcholine (ACh), dopamine (DA), and serotonin (5HT) in rat brain, significantly enhanced the performance of rats and mice in several behavioral test procedures. At doses of 0.01–0.1 mg/kg s.c. DuP 996 protected against a hypoxia‐induced passive avoidance deficit in rats. In active avoidance procedures, DuP 996 enhanced acquisition of responses: in rats, at doses between 0.085 and 0.85 mg/kg s.c. and 0.25 and 0.85 mg/kg p.o.; in mice, at doses between 0.85 and 2.5 mg/kg s.c. These effects occurred without any alteration of sensitivity to foot‐shock. In addition, Dup 996 prevented a CO2‐induced retention deficit of a passive avoidance response when administered prior to acquisition testing. In a test for acquisition of lever pressing for food in the rat, DuP 996 increased the proportion of animals acquiring this response. Thus, DuP 996 was active in both the shock‐ and appetitive‐motivated procedures and was shown to enhance performance levels when administered post‐training as well as before training trials. These results suggest that DuP 996 may be useful in the treatment of cognition dysfunction.
Pharmacological validation of ritanserin and risperidone in the drug discrimination test procedure in the rat
Authors: Meert Theo F. , De Haes Patrick L. A. J. , Vermote Patrick C. M. , Janssen Paul A. J. 
Published: January 2005

AbstractThe results presented here indicate that 0.16 mg/kg LSD, 2.50 mg/kg 8‐OHDPAT, 1.25 mg/kg d‐amphetamine, 10.00 mg/kg cocaine, 40.00 mg/kg chlordiazepoxide, 2.50 mg/kg xylazine, and 0.04 mg/kg fentanyl can be used as discriminative stimuli in a two‐lever drug discrimination test procedure in the rat. The central 5‐HT2 antagonist ritanserin and the 5‐HT2 and catecholamine (CA)‐antagonist risperidone were tested for stimulus generalization with, and possible antagonism of, the discriminative stimulus properties of the various training drugs. With both drugs at all doses tested, no stimulus generalization was observed with any of the training drugs. Ritanserin completely blocked the discriminative stimulus properties of LSD at 40.00 mg/kg but was, at doses up to 40.00 mg/kg, unable to block the discriminative stimulus properties of any of the other training drugs. Risperidone completely antagonized the stimulus properties of LSD and d‐amphetamine, partially blocked cocaine, and possessed minor effects on 8‐OHDPAT and fentanyl. Whereas ritanserin was almost without any effects or response rate, risperidone mostly reduced response rate at doses starting between 0.16 and 0.63 mg/kg. However, the complete antagonism of the LSD and d‐amphetamine was observed without effects on response rate. Globally, these results confirm ritanserin to be a selective 5‐HT2 antagonist without any effects on conditioned behaviour. Risperidone was found to be a potent 5‐HT2 and DA antagonist, affecting conditioned behaviour by interfering with response rate and with the response‐reinforcement contingency.
Monosialogangliosides (GM1 and AGF2) reduce acute ethanol intoxication: Sleep time mortality, and cerebral cortical Na+, K+‐ATPase
Authors: Hungund Basalingappa L. , Reddy Mary V. , Bharucha Vandana A. , Mahadik Sahebarao P. 
Published: January 2005

AbstractGanglioside pretreatment of mice reduced the sleep time, mortality, and loss of cerebral cortical membrane Na+, K+ ‐ATPase associated with acute ethanol treatment. Gangliosides GM1 and AGF2 (an internal ester of GM1) were optimally effective at a dose of 20 mg/kg when injected 24 hr and 1 hr prior to ethanol injection (3 mg/kg). Blood ethanol levels were slightly lower in GM1‐ and AGF2‐pretreated mice than in the saline‐ethanol group. The sleep times of GM1‐ and AGF2‐injected mice were 32 ± 10 min and 34 ± 12 min respectively vs. 58 ± 15 min for saline‐ethanol‐treated animals. Mortality was 64% and 34% in animals pretreated with GM1 or AGF2 and ethanol, respectively, while in animals treated with saline and ethanol the mortality was 80%. No decrease in crotical membrane Na+, K+ ‐ATPase was seen at 15 min or 40 min after ethanol administration in animals pretreated with AGF2. The decrease in cortical membrane ATPase from GM1‐treated animals was similar to losses in saline‐ethanol‐treated animals (25% after 15 min and 40% min). Pretreatment with either AG4 (asialo GM1) or sialic acid did not affect any of the parameteres tested.
Neuroleptics produce within‐session response decrements: Facts and theories
Authors: Fowler Stephen C. 
Published: January 2005

AbstractAcute neuroleptic administration results in within‐session decrements for conditioned active avoidance, discriminated lever release (reaction time), fixed‐ratio responding, lever pressing for intracranial electrical stimulation, licking, runway running, and treadmill running. Similarly, catalepsy has been shown to be increased by repeated testing. This paper briefly reviews these findings and reports new results on the effects of haloperidol on the micro‐characteristics of rats' operant behavior maintained by fixed‐ratio 20 food reinforcement. With these methods, within‐session decrements were seen to be produced by abrupt cessation of responding and by response slowing that was evident from the first few responses in the session. It is argued that within‐session decrements can be viewed as manifestations of neuroleptic‐induced pseudoparkinsonism in the rat and that dynamic neurochemical changes in the nigrostriatal dopamine system mediate the behavioral changes.
Drug discrimination and drug stimulus generalization with anxiolytics
Authors: Ator Nancy A. 
Published: January 2005

AbstractWork with lorazepam in two‐lever food‐maintained drug discrimination procedures with baboons and rats found greater specificity in the generalization profile when this drug was used as a training drug compared to studies with other benzodiazepines (BZ). That is, animals trained to discriminate lorazepam have not reliably made the drug response in tests with barbiturates, although animals trained to discriminate diazepam, chlordiazepoxide, triazolam, oxazepam, and sometimes midazolam commonly have done so. Characterization of the discriminative stimulus effects of lorazepam has included manipulation of species, training dose, and route of administration; drug interaction studies; and tests with a variety of anxiolytics. The time course of the discriminative stimulus effects of lorazepam and other drugs also has been studied using a multiple session procedure in baboons. Some of these results have provided information relevant to the extent to which intermediate levels of the drug response in test sessions at doses that do not reduce response rates may meaningfully reflect threshold or partial drug stimulus effects.
Stimulus functions of drugs and the assessment of abuse liability
Authors: Brady Joseph V. , Hienz Robert D. , Ator Nancy A. 
Published: January 2005

AbstractThe development of a unifying framework for conceptualizing the commonalities in various forms of substance abuse must encompass the data base focused upon the stimulus functions of drugs. In the first instance, for example, the research on drug self‐administration has provided convincing evidence of a remarkable concordance between laboratory animals and human substance abusers in the reinforcing stimulus functions of a range of chemical agents. The recognition of these cross‐species and cross‐drug generalities has radically changed conceptualizations of substance abuse from a reactive to a more active process and has encouraged the kind of functional analysis of drug‐seeking and drug‐taking that has proven productive and useful in the study of other behavioral interactions. In this regard as well, recent refinements in the analysis of the discriminative stimulus functions of drugs have provided a more comprehensive basis for characterizing a chemical agent's spectrum of action and evaluating its abuse liability. While the correlation between the discriminative stimulus functions and the reinforcing stimulus functions is remarkably high for some drug classes, there are notable exceptions. Finally, the assessment of abuse liability requires an analysis of the eliciting stimulus functions of drugs as reflected by the physiological and behavioral changes, both acute and chronic, that follow drug administration. The methods used to evaluate both physiological dependence and behavioral toxicity in relationship to sensory and motor effects for a range of abused drugs have depended heavily upon an assessment of the eliciting stimulus functions of such compounds.