bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholecystokinin octapeptide prevents extinction of active avoidance behavior in the rat
Authors: Itoh Shinji , Katsuura Goro 
Published: January 2005

AbstractThe effect of cholecystokinin octapeptide (CCK‐8) on the performance of platform‐jumping avoidance behavior was investigated in the rat. CCK‐8 was injected subcutaneously once in different doses immediately after training trials. The number of avoidance responses remained high 5 and 10 days after the CCK‐8 administration and the greatest effect was observed with doses of 10 and 100 ng/kg, while in control saline group the number of responses decreased after 5 days. Larger doses of CCK/8 were less effective, probably due to a sedative action.
New perspecties on the phusiology, chemistry, and pharmacology of memory
Authors: Lynch Gary , Larson John , Staubli Ursula , Baudry Michel 
Published: January 2005

AbstractConsiderable progress has been made in the analysis of learning and memory both at the level of the chemical processes involved in translating brief phusiological events into long‐lasting changes in synaptic efficacy and at the level of the location of the changes responsible of behavioral phenomenon of memory. This review focuses primarily on recent findings concerning the phenomenon of long‐term potentiation (LTP) of synaptic transmission elicited in hippocampal pathways by certain patterns patterns of electrial stimulation of various pathways. We first discuss the nature of the physiological events which are critically involved in LTP induction and indicate that these events are linked with naturally occurring patterns of activity in behaving animals. Detailed analysis of the physiological events taking place in the initial period of LTP induction points out a very specific sequence of biochemical/biophysical mechanisms that play a critical role in triggering LTP. We then briefly review the evidence indicting that LTP induction is accompanied by various types of structural modifications that have been proposed to be responsible for the long duration of the synaptic changes. This is followed by the description of a candidate biochemical mechanism that links the initial events triggered by LTP‐inducing stimulations and the long‐lasting modifications in synaptic structure and function. The final section presents our efforts to situate the analysis of the LTP phenomenon in the broader context of learning and memory and in particular indicates how the knowledge obtained at the biochemical and cellular level can be used to design new strategies for a pharmacological analysis of the memory processes.
Quantification of the morphine reversal activity of opioid agonists/antagonists and naloxone by using a rabbit tooth pulp procedure
Authors: Wynn Richard L. , Bergman Stewart A. 
Published: January 2005

AbstractThe rabbit tooth pulp procedure was used to determine the potencies and durations of morphine reversal by naloxone, buprenorphine, nalbuphine, butorphanol, and pentazocine. Cumulative doses (mg/kg) required to double the number of morphine‐depressed respirations per minute (RPM) (ED 2 X) and to reduce morphine‐elevated lick/chew (L/C) volts by one‐half (ED 1/2) were determined. These doses were naloxone 0.003, 0.013; buprenorphine 0.030, 0.130; nalbuphine 0.130, 0.520; butorphanol 0.120, 0.630; pentazocine 1.10, 0.150. The antinociceptive effects of these compounds were compared by determining the cumulative dose required to achieve the highest percentage maximum possible effect (% MPE) as determined by the elevation of lick/chew threshold volts from control volts in morphine‐free rabbits: naloxone 6% at 0.0005 mg/kg; buprenorphine 69% at 0.075 mg/kg; nalbuphine 32% at 0.150 mg/kg; butorphanol 32% at 0.150 mg/kg, and pentazocine 12% at 1.55 mg/kg. The durations (min) of reversal of morphine RPM and morphine L/C volts were also determined: naloxone 33, 30; buprenorphine 240, 240; nalbuphine 120, 120; butorphanol 90, 45; pentazocine 60, 15. It is suggested that the rabbit tooth pulp assay is a sensitive and reliable assay to evaluate and quantitate compounds for opioid agonist/antagonist activity.
Small peptides and nerve growth: Therapeutic implications
Authors: Taylor J. E. , Moreau J. P. , DeFeudis F. V. 
Published: January 2005

AbstractStudies of the effects of small peptides (<10,000 Da), i.e., fragments of naturally occurring hormones (e.g., adrenocorticotrophic hormones [ACTH]: α‐melanocyte‐stimulating hormone [α‐MSH]), hypophysiotrophic factors (e.g., growth hormone‐releasing hormone [GHRH], thyrotropin‐releasing hormone [TRH]), other growth factors, and synthetic compounds on peripheral and CNS neuronal regeneration and behavior have been reviewed and analyzed. It seems apparent that certain hormonal fragments, growth factors, and some synthetic compounds (e.g., the ACTH/α‐MSH analogue Org 2766) can enhance peripheral, and possibly CNS, nerve regeneration. Further study of newer peptide‐analogues with increased potency, longer duration of activity, and greater selectivity of action might lead to the development of therapies for certain types of nerve injury and for neurodegenerative disorders.
Effect of ipratropium bromide on bronchospasm induced by inhalation of hypotonic solutions
Authors: Neria José Pérez , Montaño R. Luis Manuel , Monge L. Gilberto , Rubio M. Horacio , Selman L. Moisés 
Published: January 2005

AbstractIn order to determine the role of the cholinergic system in the bronchoconstriction induced by hypotonic solutions 30 subjects were studied: 15 asthmatic patients and 15 healthy volunteers to whom distilled water was administered by inhalation through ultrasonic nebulization. All asthmatic patients showed a 20% reduction of forced expiratory volume in 1 sec in relation to the initial value. Bronchospasm was not detected in any of the healthy subjects. After 24 hr, ipratropium bromide in aerosol was administered 1 hr before distilled water nebulization, and this prevented the bronchoconstriction response in 11 of the 15 asthmatic patients. These results suggest that such bronchospasm is mediated at least in part by vagal reflex.
Pharmacological evaluation of HP 370, a potential atypical antipsychotic agent: 1. In vivo profile
Authors: Szewczak Mark R. , Cornfeldt Michael L. , Dunn Robert W. , Wilker Jeffrey C. , Geyer Harry M. , Fielding Stuart , Glamkowski Edward J. , Chiang Yulin 
Published: January 2005

AbstractHP 370 4,9‐Dibromo‐6‐(4 methyl‐1‐piperaziny(l)benzo((b)pyrrolo[3,2,1‐jk][1,4 benzodiazepine] demonstrated preclinical activity indicative of clinical atypical antipsychotic activity, which may provide an advantage over current therapeutic agents. It was effective in blocking apomorphine‐induced climbing behavior in mice (ED50 = 4.1 mg/kg i.p.; 1.6 mg/kg p.o), locomotion caused by direct application of dopamine to the nucleus accumbens in rats (ED50 = 15.4 mg/kg i.p.), intracranial self‐stimulation in rats (ED50 = 10.1 mg/kg i.p.), and pole‐climb avoidance in rats (ED50 = 4.0 mg/kg p.o. avoidance; 10.6 mg/kg p.o. escape failures). HP 370 was relatively inactive in blocking aporomorphine‐induced stereotypy in rats (50% at 40 mg/kg, 33% at 20 mg/kg i.p.), relatively inactive in causing catalepsy in rats (50% at 40 mg/kg i.p.)m and was completely inactive in blocking stereotypy caused by the direct application of dopamine to the corpus striatum of rats (up to 80 mg/kg i.p.). Chronic administration of HP 370 caused supersensitivity to apomorphine in the climbing mouse test and in dopamine‐induced locomotion in rats, but not in dopamine‐induced stereotypy in rats. Acute administration of HP 370 caused and increase in the numberof active dopamine neurons sampled in both the ventral tegmental area and substantia nigra of rats, whereas chronic administration resulted in singnificantly fewer dopamine neurons found in the ventral tegmental area with no change from control levels observed for the substantia nigra. In a measure of social interaction in rats, HP 370 significantly increased the time spent interacting without altering overall activity, suggesting favorable effects on negative symptomatology. No in vivo anticholinergic activity was seen in the physostigmine lethality test in mice. In vivo blockade of alpha noradrenergic receptors was suggested by the inhibition of norepinephrine lethality in rats (50= 0.6 mg/kg i.p.). HP 370 displays an in vivo profile consistent with that of an atypical antipsychotic agent and is predicted to be clinically effective with fewer side effects than currently available therapy.
Cardiovascular profile of the cardioselective beta‐adrenoceptor antagonist bisoprolol in anesthetized pigs
Authors: Verdouw Pieter D. , Schmeets Iiona O. L. , Rensen Rob J. 
Published: January 2005

AbstractThe cardioselective beta‐adrenoceptor antagonist bisoprolol ((±)−1‐[4‐(2‐isopropoxyethoxy‐ymethyl)‐phenoxy]3‐isopropylamino‐2‐propanol‐hemifumarate, EMD 33512) was studied for its effects on cardiac performance in ten anesthetized open‐chest pigs. Radioactive labelled microspheres (15 ± 1 μm) were used to determine regional blood flows. In doses of 4, 16, 64, 256, and 1,024 μg · kg−1 (arterial plasma concentrations 1.65 ± 0.07 to 569 ± 22 ng · ml−1) the drug caused dose‐dependent decreases in cardiac output (4–31%, P < .05) that were primarily due to a negative chronotropic action as heart rate, which had already been slowed down by 9% (p < .05) after the lowest dose, decreased up to 22% (p < .05). Stroke volume was not significantly affected at any dose, although it tended to decrease after the highest dose of hisoprolol (−10%, p < .05). Myocardial it tended to reflected by maxLVdP/dt, fell dose dependetly from 12% (after 4μg · μg·Kg−1, P < .05) up to 46% (after 1,024 μg · −1, P < .05). Raising the heart rate to predrug levels revealed that this reduction in maxLVdP/dt was not related to the bradycardic action of the drug. Mean arterial blood pressure decreased slightly (<15%, P < .05) after the highest three doses, but a larger fall was prevented by a mild vasoconstriction of the systemic arterial vascular bed as systemic vasular resistance increased up to 28% (P < .05). Pulmonary artery pressure was not affected, because pulmonary vasuclar resistance increased with the highest doses. Left ventricular blood flow, which had already decreased significantly with the lowest dose (11%, P B < .05), also decreased dose dependently (up to 44% after 1,024 μg · kg−1, P < .05). These decreases were equally distributed over all myocardial layers as the endolepi blood flow ratio (1.13 ± 0.04) was not affected. Myocardial 02 consumption was not affected by the lowest dose, but decreased progressively up to 43% (P <
.05) with the higher doses. These changes occurred parallel to those in blood flow as myocardial O2 extraction did change. Cerebral blood flow was well preserved but decreases in perfusion of some other organs and tissues (kidneys, stomach, and skeletal muscle) were similar to those in cardiac output.In conclusion, bisoprolol has a cardiovascular profile similar to that of other beta‐adrenoceptor agents. The finding that no serious adverse cardiovascular affects are observed over a wide dose range warrants further studies in models of myocardial is‐chemia and hypertension.
Preventive effect of cholecystokinin octapeptide on scopolamine‐induced memory impairment in the rat
Authors: Itoh Shinji , Takashima Akira , Katsuura Goro 
Published: January 2005

AbstractIn a passive avoidance response, intraperitoneal administration of scopolamine (0.5 mg/kg) at 15 min before the training trials produced a marked impairment of memory in the rat. However, pretreatment with cholecystokinin octapeptide (CCK‐8) either given subcutaneously or intracerebroventriculary (i.c.v.) prevented the scopolamine‐induced amnesia. Continuous i.c.v. infusion of CCK‐8 (1 ng/day) for 7 days significantly prevented the amnesia. The results support our previous findings that CCK‐8 has a protective effect against experimental amnesia in the rat.
New potential antipsychotic drug BMY 20661: A profile of its effects on midbrain dopamine neurons
Authors: Henry Douglas J. , White Francis J. 
Published: January 2005

AbstractThe new potential antipsychotic drug BMY 20661 was subjected to a series of electrophysiological tests to determine its effects on midbrain dopamine (DA) neurons in the rat substantia nigra pars compacta (A9) and ventral tegmental area (A10). Acute intravenous (i.v.) administration of BMY 20661 exerted little effect on the basal spontaneous firing rates of either A9 or A10 DA neurons. Following suppression of DA unit activity by the DA agonist apomorphine (APO), BMY 20661 consistently increased the firing of A10, but not A9, DA cells. However, the rates of A10 DA cells seldom recovered to pre‐APO basal levels following BMY 20661 administration. The ability of BMY 20661 to partially reverse the APO‐induced rate suppression was apparently not due to blockade of DA receptors since pretreatment with BMY 20661 (6.3 mg/kg, i.v.) only slightly (nonsignificantly) reduced the ability of APO to inhibit the firing of A10 cells. Surprisingly, BMY 20661 significantly attenuated the effects of APO on A9 DA cells. These findings suggest that BMY 20661 influences A10 DA neurons by a non‐DA mechanism. Because BMY 20661 has been reported to bind to 5‐HT1A receptors, the acute effects of this compound were compared to those of 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT), a known 5HT1A agonist. These compounds demonstrated similar profiles in their ability to reverse APO‐induced suppression of A10 DA cells but, unlike BMY 20661, 8‐OH‐DPAT was also active on A9 DA cells. Repeated administration of BMY 20661 for 28 days (either 5 or 10 mg/kg/day) failed to alter significantly the number of spontaneously active A10 DA cells but caused a small, but statistically significant, increase in the number of A9 DA cells/track. Because the ability to decrease the number of spontaneously active A10 DA cells has been proposed as a predictive model for antipsychotic drug action, the results obtained following repeated administration of BMY 20661 fail to support a potential antipsychotic profile for this new compound.
Neurochemical and behavioural profile of Lu 17‐133, (±)‐trans‐4‐[3‐(3,4‐dichlorophenyl)‐indan‐1‐yl]‐1‐piperazineethanol, an inhibitor of the uptake of dopamine and noradrenaline
Authors: Hyttel J. , Arnt J. , Bøgesø K. , Christensen A. V. , Larsen J.‐J , Lembøl H. L. , Meier E. , Sánchez C. 
Published: January 2005

AbstractThe neurochemical and behavioural profile of Lu 17‐133, (±)‐trans‐4‐[3‐(3,4‐dichlorophenyl)‐indan‐1‐yl]‐1‐piperazineethanol has been characterized and compared with that of a series of inhibitors of biogenic amine uptake. Lu 17‐133 inhibits the uptake of dopamine and noradrenaline in the nanomolar range, but it has only a weak effect on serotonin uptake. Blockade of receptors for dopamine (D‐1, D‐2), noradrenaline (α1, α2), histamine (H1), acetylcholine (muscarinic), and serotonin (5‐HT2) was absent or seen only at micromolar concentrations. The biochemical profile is close to that of GBR 13.069, GBR 12.921, and Lu 19‐005 (INN name, Indatraline). Lu 17‐133 shows only weak behavioural effects. In high doses, it potentiates apomorphine and 5‐HTP and reverses the effect of tetrabenazine in mice. It has minimal stimulatory property, as it increases very weakly the locomotor activity in mice and does not induce stereotypy (either low‐component or oral stereotypy) in rats. It does not induce ipsilateral circling behaviour in 6‐OHDA‐lesioned rats, although in combination with scopolamine, a full ipsilateral rotation is seen. Lu 17‐133 has no anticataleptic effect and does not generalize to the discriminative stimulus properties induced by d‐amphetamine. Experiments have shown that there is no clear correlation between inhibitory effect on dompamine uptake and in vivo effects in the models detecting dopamine‐stimulating compounds; nor is there any obvious correlation between effects in different in vivo test models. The neurochemical and behavioural characteristics of Lu 17‐133‐inhibition of dopamine‐ and noradrenaline‐uptake in vitro with low stimulatory properties in vivo make it an interesting candidate as a new antidepressant drug.
Prevention of scopolamine effect on the decrease of acetylcholine content by peripherally administered cholecystokinin octapeptide in some regions of the rat brain
Authors: Takashima Akira , Itoh Shinji 
Published: January 2005

AbstractIntraperitoneal injection of scopolamine at a dose of 0.5 mg/kg produced a marked decrease after 15 min in the acetylcholine (ACh) content of the frontal and temporal cortices and the hippocampus in the rat. In the parietal and occipital cortices and the striatum, the decrease in ACh content was less extensive. When rats were treated with cholecystokinin octapeptide 15 min before the scopolamine administration, the decrease in ACh was prevented in a dose‐dependent manner. The choline content was not affected significantly by these treatments.
Cholinergic systems and alzheimer's disease
Authors: Defeudis F. V. 
Published: January 2005

AbstractStudies of central cholinergic mechanisms, cholinergic drugs, and Aizheimer's disease (AD) have been reviewed and analyzed. Although the pronounced cholinergic deficit that exists in the brains of AD patients is associated with memory loss and other cognitive dysfunctions, cholinergic “replacement therapy” is of limited benefit in trating AD. Recent findings concerning the roles of nerve growth factor, “excitotoxic” amino acids, and amyloid deposition in AD migh lead to mroe fruitful therapeutic approaches.
A double‐blind, placebo‐controlled study with oxiracetam in demented patients administered the Luria‐Nebraska Neuropsychological Battery
Authors: Mangoni A. , Perin C. , Smirne S. , Piccolo I. , De Filippi F. , Marchetti C. , Motta A. , Monza G. C. 
Published: January 2005

AbstractA formal multicenter, double‐blind, between‐patient trial was carried out to evaluate the efficacy and tolerability of oxiracetam (OXIR) (800‐mg tablets), in comparison with placebo, each given twice daily for 24 weeks to patients suffering from probable or possible Alzheimer's disease (AD). Efficacy was assessed by the Inventory of Psychic and Somatic Complaints in the Elderly (IPSC‐E), administered at entry and after 8, 16, and 24 weeks of treatment, and by the Luria‐Nebraska Neuropsychological Battery (LNNB), administered at the beginning and at the end of the study. Thirty patients (16 on OXIR and 14 on placebo), 20 males and 10 females, mean age 62 years (range 52–79), were enrolled and completed the study. A significant (P < 0.01) difference between treatments in the total score of the IPSC‐E, as well as in some LNNB scales, was observed. In particular, patients on OXIR showed an improvement over time, while the condition of patients on placebo remained unchanged or tended to get worse. No difference in tolerability between the active drug and placebo was observed.
Effect of vinpocetine on monoamine receptor binding and synaptosomal uptake in the rat brain
Authors: Lee David K. H. , Geiger G. 
Published: January 2005

AbstractThe in vitro effect of vinpocetine on the various adrenergic, serotoninergic, and dopaminergic receptor systems was studied in the rat. At 1 μM concentrations, vinpocetine and its major metabolite, apovincaminic acid, did not exhibit inhibitory activity in any of the receptor binding assays, nor did vinpocetine show any significant inhibitory effect in the synaptosomal uptake assays at ten‐fold higher concentrations. The results suggest the unlikeliness that vinpocetine exerts its pharmacological effects through monoamine receptor binding or synaptosomal uptake mechanisms.
Effect of aniracetam and the benzodiazepine receptor partial inverse agonist Ro 15‐3505 on cerebral glucose utilization and cognitive function after lesioning of cholinergic forebrain nuclei in the rat
Authors: Lorez Hans‐Peter , Martin James R. , Keller Hans H. , Cumin Rudolf 
Published: January 2005

AbstractRegional cerebral [3H]2‐deoxyglucose uptake, choline acetyltransferase (ChAT) activity, monoamine levels, and cognitive performance—and the modulation thereof by drugs—were studied in rats after electrolytic lesion of the nucleus basalis magnocellularis (NBM) and septum. The animals showed long‐lasting memory impairment in a passive avoidance task as well as degeneration of cholinergic and monoaminergic nerve terminals in the neocortex (after NBM lesion) and hippocampus (after septum lesion). The denervated regions showed a long‐lasting reduction of the uptake of [3H]2‐deoxyglucose, indicating a decreased glucose utilization rate. The pyrrolidinone derivative aniracetam (Ro 13‐5057) and the benzodiazepine receptor partial inverse agonist Ro 15‐3505 improve cognitive functions in various animal tests. Rats with bilateral NBM lesions that typically exhibited passive avoidance learning, but no retention 24 hr later, were administered aniracetam, Ro 15‐3505, physostigmine, or tetrahydroaminoacridine after the acquisition phase. Ro 15‐3505 and physostigmine produced the most convincing ameliorative effects. Aniracetam did not change the cerebral glucose utilization in either control rats or in NBM or septumlesioned rats. In contrast, Ro 15‐3505 increased glucose use in various brain regions of control animals by 10–30% and partially reversed the deficit in lesioned animals. The effect of Ro 15‐3505 on glucose utilization and passive avoidance retention may be related to the disinhibition of various neuronal circuits; however, fully intact cholinergic and monoaminergic innervation of the cerebral cortex and hippocampus is not a prerequisite.
Beneficial effects of idebenone on memory impairment in rats
Authors: Nagaoka A. , Nagai Y. , Yamazaki N. , Miyamoto M. , Kiyota Y. 
Published: January 2005

AbstractIdebenone showed beneficial effects on memory impairments in the passive avoidance, radial maze, and T‐maze tests in rats with cerebral ischemia, cerebral infarction, basal forebrain lesions, and treatment with an anticholinergic drug. The drug ameliorated neurological deficits following the onset of cerebrovascular lesions in strokeprone rats. In the neurochemical study, idebenone normalized reduced levels of 5‐hydroxy indole acetic acid (5‐HIAA) and acetylcholine (ACh) in various regions of the brain and inhibited the decrease in adenosine triphosphate (ATP) and the increase in lactate that occurs after cerebral ischemia. Furthermore, the drug activates mitochondrial respiratory function and inhibits lipid peroxidation in brain tissue. From these results, it is suggested that idebenone primarily ameliorates the energy failures in damaged brain tissues, partially normalizes the altered neural transmission in the tissues, and improves memory disturbance in rats.