bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional relationships between the immune and central nervous systems in Alzheimer's disease
Authors: Kozlowski Gerald P. , Nilaver Gajanan 
Published: January 2005

AbstractAn intact blood–brain barrier (BBB) is a prerequisite to maintaining functional compartmentalization between the neural and immune systems. Only small amounts of immunoglobulins access the internal milieu of the brain, probably via so‐called “functional leaks” existing in the region of the circumventricular organs. However, with aging and disease, globular and other proteins can be found within the cerebrospinal fluid (CSF) because of disruption of perhaps both the BBB and the blood–CSF barrier. There is an increase of lgG, IgA, albumin, and prealbumin in CSF of patients with Alzheimerapos;s disease. The presence of these proteins is taken to be pathognomonic for neuronal impairment, and they are believed to be associated with the amyloid deposits of senile plaques. Our studies have shown that albumins may occur naturally in some CNS neurons. Immunocytochemical studies with antibodies to rat serum albumin have shown the uptake of this serum protein by nerve endings with retrograde transport to perikarya of their cells of origin. Likewise, we have also shown than an endogenous albuminoid substance occurs in arcuate nucleus neurons of the hypothalamus that immunoreact with antibodies to bovine serum albumin. The arcuate nucleus neurons are neurosecretory and have neurohemal endings in contact with blood vessels of the hypothalamohypophysial vasculature. These neurohemal contacts are capable of taking up albumins from the blood for retrograde transport. We, therefore, hypothesize that immunoglobulins may be similarly incorporated by neurons having neurohemal contacts and access the CNS in this and several other ways. We have localized endogenous gammaglobulins in brains of both immunized and nonimmunized rabbits with antisera against rabbit lgG generated in sheep, goat, and mouse. However, serum proteins are also found in neurons without neurohemal contacts. Taken together, albumins, globulins, and other substances may reach the interior milieu of the CNS via: (1) endothelial transcytosis, (2) neurohemal contacts whereby neurons take up blood‐borne substances and retrogradely transport them to their perikarya, (3) circumventricular organs (inter‐ and intraependymal transport), (4) functional leaks at the interface of the circumventricular organs and the brain, (5) a nose–brain pathway, (6) a meningeal pathway, and (7) transsynaptic transport, i.e., substances passed from a neurohemal cell to other connecting neurons.
Antibodies recognizing cholinergic neurons and thyroglobuline are found in the cerebrospinal fluid of a subgroup of patients with Alzheimer's disease
Authors: McRae‐Degueurce Amanda , Haglid Kenneth , Rosengren Lars , Wallin Anders , Blennow Kaj , Gottfries C.‐G. , Dahlström Annica 
Published: January 2005

AbstractThe presence of cholinergic neuron specific lgG in the CSF of a subgroup of patients with Alzheimerapos;s disease (AD) was demonstrated by immunocytochemistry. The lgG labeled cholinergic nerve cell bodies in the medial septum of rat brains, perfusion fixed with glutaraldehyde/allyl alcohol to fix small transmitter molecules. Many of the patient CSFs also recognized thyroglobuline in an ELISA assay. Antithyroglobuline furthermore recognized the same cholinergic neurons in the rat brain as the CSF and antiacetylcholine, as did anti‐T3 and anti‐T4. The results indicated that in a subgroup of AD patients autoimmune mechanisms may play a role in the pathogenesis of dementia, and that disturbances in the handling of thyroid hormone in the CNS may be involved in the disease process.
Nzb mouse: Hippocampal mossy fiber patterns and behavioral profiles of young and older animals
Authors: Schwegler H. , Lipp H.‐P. , Crusio W. E. 
Published: January 2005

AbstractNew Zealand Black mice (NZB) are widely used as a model for presenile dementia, because an autoimmune disease induces early senescence in these animals. Since some of the behavioral properties of NZB might also be related to normal, nonpathologic variations in brain morphology, NZB of different age groups were tested in a number of hippocampus‐dependent tasks. As control strain we used the non‐autoimmune strain C57BL/6. In addition to behavioral testing, we measured the sizes of the hippocampal regio inferior (CA3 + CA4) and the intra‐ and infrapyramidal mossy fiber terminal fields. NZB mice were inferior to C57BL/6 in active one‐way avoidance and performed poorly in a radial maze. For learning scores in other behavioral paradigms NZB mice showed performance levels comparable to other fair‐ to well‐performing strains. Slight age‐related declines in NZB, but not in C57BL/6, mice could be observed in most learning tasks. The hippocampal regio inferior is larger in NZB than in C57BL/6, whereas the latter mice have much larger infrapyramidal mossy fiber (iip‐MF) terminal fields. From this and from previous data it appears that at least some of the behavioral differences between NZB and C57BL/6 may reflect an influence of a factor related to the iip‐MF projection. The inclusion of strain DBA/2 in future studies is suggested.
Renal, cardiac, and systemic hemodynamic effects of the dopamine receptor agonist SK&F 85174 in anesthetized dogs
Authors: Dlewati Abdallah , Lokhandwala Mustafa F. , Chelly Jacques E. , Doursout Marie‐Francoise 
Published: January 2005

AbstractSK&F 85174 is a mixed DA‐1/DA‐2 receptor agonist which is shown to inhibit sympathetic neurotransmission and cause hypotension in anesthetized animals. In this study, we have determined the regional and systemic hemodynamic effects of an intravenous infusion of SK&F 85174 (5 μg/kg/min for 5 min) in pentobarbital‐anesthetized dogs and attempted to identify the dopamine receptor subtype(s) involved in the cardiac as well as vascular effects of this compound. SK&F 85174 produced significant decreases in mean blood pressure (MBP), left ventricular pressure (LVP), left ventricular dp/dt, total peripheral resistance (TPR) and renal vascular resistance (RVR), and a significant increase in renal blood flow (RBF). There were no significant changes in heart rate, cardiac output, coronary blood flow, or coronary vascular resistance. Prior treatment with SCH 23390 (DA‐1 receptor antagonist) significantly attenuated the effects of SK&F 85174 on MBP, LVP, TPR, RBF, and RVR. In a second group of dogs S‐sulpiride (DA‐2 receptor antagonist) significantly antagonized the effects of SK&F 85174 on MBP, LVP, and dp/dt, but did not influence its effects on RBF, TPR, and RVR. These results show that (a) a decrease in total peripheral resistance and not the cardiac output accounts for the hypotensive action of SK&F 85174, (b) the renal hemodynamic effects of SK&F 85174 are mediated primarily via the activation of DA‐1 receptors, and (c) whereas DA‐1 receptors are involved primarily with the hypotensive action of this compound, it appears that activation of DA‐2 receptors also contributes to the hypotension.
Effects of reinforcement on stimulus control of drug discrimination behavior
Authors: Mathis D. A. , Emmett‐Oglesby M. W. 
Published: January 2005

AbstractThe present study was designed to examine the disruptive effects of reinforcement during stimulus onset/offset in drug‐discrimination tasks. Rats were trained on a two‐lever task to discriminate either pentylenetetrazole (PTZ, 20 mg/kg) or cocaine (CN, 10 mg/kg) from saline, with food used as a reinforcer. Tests for onset of the drug stimulus were conducted immediately after an i.p. injection of the training stimulus. In order to test drug offset, rats trained to discriminate PTZ were tested immediately after an injection of diazepam (DZP, 5 mg/kg) given 15 min after an injection of PTZ. Responses on either lever were reinforced throughout the 20‐min session. Although the onset or offset of a drug stimulus significantly changed lever selection, consistent change in lever selection was obtained from approximately 30% of the subjects. For both the CN and PTZ onset groups, lever changing occurred after either (1) a disruption in responding, which produced a period of no reinforcement, or (2) very early in the session, which provided only brief exposure to reinforcement for responding on the other lever. Drug‐induced disruption of behavior was much more apparent during PTZ onset than during CN onset. For animals that continued to be reinforced for nondrug responding after onset of the drug stimulus, discrimination of the training stimulus during subsequent training was not disrupted by the testing procedure.
Limitations of existing theory in explaining state‐dependent performance of rats on the maier three‐table reasoning problem
Authors: Stahl Jeanne Marsh , Pieper Walter Alan 
Published: January 2005

AbstractThe three‐table reasoning problem was developed by Norman Maier in 1929 to test the ability of rats to combine the essentials of two isolated experiences to reach a goal. The purpose of this paper is to describe the test situation and the performance of rats that were given each experience in a different chemical state prior to testing. Rats given morphine, methadone, or naloxone for both experiences and the test performed well on this task, whereas rats given the first experience in an undrugged or saline condition and given the second experience in a morphine, methadone, or naloxone condition performed poorly. Similarly, rats given experience 1 in a undrugged condition, experience 2 in a morphine or methadone condition, and the test in a naloxone condition performed poorly. Although these results cannot be explained by most theories of state‐dependent learning, an interpretation is presented, with suggestions for further research.
Yohimbine and serotonergic agonists: Stimulus properties and receptor binding
Authors: Winter J. C. , Rabin R. A. 
Published: January 2005

AbstractThe present investigation was designed to compare the discriminative stimulus properties of yohimbine and purported agonists at the serotonin (5‐HT)1A receptor. To that end, groups of rats were trained with yohimbine, 8‐OH‐DPAT, and ipsapirone, respectively. Tests of generalization were then conducted, and the interaction between clonidine and yohimbine was examined. Drugs examined behaviorally were also characterized in terms of their relative affinities at the 5‐HT1A, 5‐HT1B, and 5‐HT2 receptors by means of standard radioligand binding techniques. A high degree of generalization was observed between each of the training drugs and in tests of gepirone and buspirone. Comparisons of the behavioral and receptor binding data argue against stimulus control mediated solely by a 5‐HT1A‐based mechanism. The observed pattern of interaction of clonidine with yohimbine in rats trained with the latter drug suggests that clonidine may function as a partial agonist. Whatever the mechanistic basis for the present discrimination data, we are left with the puzzle of why yohimbine, widely regarded as anxiogenic, should share stimulus properties with anxiolytic drugs.
Discriminative stimulus properties of ICSS in rats: Effects of ethanol and RO 15‐4513
Authors: Schaefer Gerald J. , Michael Richard P. 
Published: January 2005

AbstractRats were implanted with stimulating electrodes aimed at the medial forebrain bundle–lateral hypothalamus and trained in a discrete trial procedure to make a differential response (right or left lever press) in the presence or absence of brain stimulation. When animals reached 95% accuracy in this discrimination, testing with vehicle, ethanol (0.1, 0.3, 0.56, 1.0, g/kg), and ethanol plus RO 15‐4513 (1.0 mg/kg) began. During test sessions intermediate stimulus currents were programmed and the data comprised the number of trials completed on the stimulation‐appropriate lever as a function of intermediate currents. The stimulus current at which 50% of the trials were completed was defined as the detection threshold. Ethanol, at 1.0 g/kg, increased the detection threshold but also increased the time to complete the session and decreased the total number of lever presses. RO 15‐4513 reversed the increase in the detection threshold and reduced the increase in time to complete the session and reduced the decreases in lever presses. However, RO 15‐4513 alone, like ethanol, increased the time to complete the session and decreased the total number of lever presses. Thus, while RO 15‐4513 reverses some of the behavioral effects of ethanol, it also has its own behavioral effects, even at low doses.
6‐Hydroxydopamine lesions of the nucleus accumbens attenuate the discriminative stimulus effects of d‐amphetamine
Authors: Dworkin Steven I. , Bimle Cindy 
Published: January 2005

AbstractTen rats were trained with a standard two‐lever procedure to discriminate d‐amphetamine (1.0 mg/kg i.p.) from saline. Training was continued until the rats emitted three or less responses on the incorrect lever before the first food presentation and more than 95% of the responses during a session occurred on the correct lever for five consecutive sessions.A descending range of doses from 1.0 to 0.17 mg/kg d‐amphetamine and saline were resulted to determine a drug‐dose generalization gradient including a threshold dose that resulted in drug‐appropriate responding. Following the determination of the threshold dose, the rats were lesioned with 6‐hydroxydopamine (6‐OHDA) or its vehicle. Three days were allowed for recovery from the lesion. The animals were then again tested starting with the threshold dose. A postlesion generalization gradient was then determined by testing the rats with increasing doses of the drug. Saline test sessions were randomly scheduled during the postlesion testing.The vehicle lesion produced a slight change in the generalization gradients. The 6‐OHDA lesion, however, resulted in a much larger attenuation in the discriminative stimulus function of the drug. Thus, it appears that destruction of the dopaminergic input into the accumbens only moderately alters the discriminative stimulus properties of d‐amphetamine.
Linogliride fumarate, an oral hypoglycemic agent, improves oral glucose tolerance in a rat model of non‐insulin‐dependent diabetes mellitus (NIDDM)
Authors: Marchione Carol S. , Tuman Robert W. 
Published: January 2005

AbstractLinogliride fumarate, a structurally novel oral hypoglycemic compound, was tested in the neonatal streptozotocin‐induced rat model of non‐insulin‐dependent diabetes mellitus (NIDDM) [Weir et al.: Diabetes 30:590–595, 1981], and its antihyperglycemic effects were compared to those of representative first and second generation sulfonylureas. Two‐day‐old male Sprague‐Dawley rats (STZ) were injected with the beta cell toxin, streptozotocin (90 mg/kg i.p.); male littermates injected with citrate buffer served as controls (CTL). By 8 weeks of age, blood glucose of fed STZ rats was significantly elevated compared to that of CTL animals (>300 mg/dl vs.<110 mg/dl, respectively) and, in response to an oral glucose (1 g/kg) challenge, 18 hr fasted STZ rats exhibited marked glucose intolerance. Linogliride fumarate (10–100 mg/kg p.o.) significantly lowered blood glucose in 18 hr fasted STZ rats and produced a dose‐dependent improvement of oral glucose tolerance. Linogliride fumarate (ED30 = 12.5 mg/kg) was approximately six times as potent as tolbutamide (ED30 = 72.1 mg/kg) in improving oral glucose tolerance in STZ rats, while glyburide (0.5–2.5 mg/kg p.o.) and glipizide (2.5 mg/kg) were ineffective. This rat model of NIDDM may be useful for evaluating new hypoglycemic compounds.
Attenuation of morphine withdrawal syndrome by macromolecular synthesis inhibitors in rats
Authors: Copeland Robert L. , Pradhan S. N. 
Published: January 2005

AbstractAttenuation of the morphine withdrawal syndrome by the combination treatment of morphine and protein/nucleic acid synthesis inhibitors was investigated in rats. Groups of rats were treated twice daily with gradually increasing doses of morphine (4–28 mg/kg) in combination with a protein/nucleic acid synthesis inhibitor (actinomycin D, chloramphenicol, cycloheximide, cytarabine, or tetracycline) for 14 days. Withdrawal was precipitated by naloxone on day 15 and the withdrawal manifestations were scored on a weighted basis for mild, moderate, and severe signs. The mild withdrawal signs were significantly decreased by cytarabine and tetracyline whereas the other combination‐treated groups were only slightly decreased. The moderate and serve withdrawal signs for all combination‐treated groups were significantly suppressed compared to the morphine‐treated group. Therefore, attenuation of the morphine withdrawal syndrome by these protein/nucleic acid synthesis inhibitors supports an involvement of macromolecules in the development of physical dependence.
Prevention of “learned helplessness” in the rat by hydroxyzine
Authors: Porsolt Roger D. , Martin Patrick , Lenégre Antoine , Fromage Sylvie , Giurgea Corneliu E. 
Published: January 2005

AbstractThe effects of hydroxyzine (8, 16, and 32 mg/kg i.p.), administered either 30 min before exposing rats to a series of inescapable shocks (preventive treatment) or during the subsequent acquisition of a shuttle box avoidance response (curative treatment), wereinvestigated. In these conditions untreated rats, previously exposed to inescapable shocks (“stress” ), show a marked increase in escape failures in the shuttle box when compared with nonshocked control animals (“ learned helplessness” ). Control experiments examined the effects of hydroxyzine on memory (passive avoidance test) and on electric shock sensitivity. Diazepam (2 mg/kg i.p.) was used as a reference compound. Hydroxyzine, when administered before “ stress,” clearly decreased at 8 and 32 mg/kg the number of escape failures observed but was without effect when administered after “stress” during the subsequent shuttle box avoidance learning. Similar results were observed with diazepam. Unlike diazepam, hydroxyzine at 32 mg/kg−1 induced no amnesia in the passive avoidance test, whereas clear amnesia was observed with diazepam. Neither compound altered the rats' sensitivity to shock. These results suggest that hydroxyzine decreases the effects of “ stress” and that these effects cannot be attributed either to impaired memory for the aversive stimulation or to diminished shock sensitivity.
Pentylenetetrazol discriminative stimuli are selective for identifying benzodiazepine receptor modulating agents
Authors: Wilson Douglas E. , Bennett Debra A. 
Published: January 2005

AbstractPentylenetetrazol (PTZ) has been reported to produce a discriminative stimulus related to anxiety and antagonized by the classical anxiolytics. In the present investigation, a variety of compounds with either benzodiazepine (BZ)‐type anxiolytic actions or other novel mechanisms of action (serotonin and N‐methyl‐D‐aspartate [NMDA] antagonism) were tested for their ability to antagonize this stimulus. Compounds that have been shown to modulate benzodiazepine receptor function were active in blocking PTZ, the discriminative stimulus. The failure of the other compounds to block these stimuli suggests that the PTZ discrimination may be selective for substances that modulate, either directly or indirectly, the BZ receptor complex.
Modification of ischemia‐induced biochemical changes in the myocardium by Rooh‐Afza extracts
Authors: Dikshit Madhu , Srivastava Ranjana , Srimal Rikhab Chand , Dhawan Bhola Nath 
Published: January 2005

AbstractIn rats, myocardial ischemia was produced by isoprenaline (80 mg/kg i.p.) and in rabbits, by ligating the anterior descending branch of the coronary artery. Two extracts of Rooh‐Afza, a Unani polypharmaceutical preparation, were administered 1 hr or 15 min before inducing ischemia. Both the extracts protected the rat myocardium from isoprenaline‐induced changes. In rabbits, protection against ischemia was observed only at a higher dose. The extract containing essential oils and flavoring agents was found to be more effective. It also inhibited platelet aggregation induced by adenosine diphosphate (ADP) in vitro and ex vivo in monkeys.
A physiologist's view of the N‐methyl‐D‐Aspartate receptor: An allosteric ion channel with multiple regulatory sites
Authors: Mayer Mark L. , Vyklicky Ladislav , Sernagor Evelyne 
Published: January 2005

AbstractWhole‐cell and single‐channel recording techniques have provided a great deal of information about the nature of the N‐methyl‐D‐aspartate (NMDA) receptor channel complex and are beginning to lead to quasimolecular models of drug action. Currently five ligand‐binding domains are known to exist on the NMDA receptor channel complex: 1) an agonist‐binding site for which structural analogues of L‐glutamate have been developed as competitive antagonists; 2) a divalent cation‐binding site within the ion channel pore, at which Mg binds to produce voltage‐dependent channel block; 3) a divalent cation‐binding site near the extracellular face of the membrane, at which Zn and Cd but not Mg bind to produce a voltage‐independent block; 4) an anaesthetic binding site within the pore, at which ketamine, phencyclidine, MK‐801, and desipramine bind with high affinity to produce voltage‐dependent ion channel block of long duration; and 5) a regulatory site on the extracellular face of the membrane at which glycine binds to promote NMDA receptor channel activity. This potentiating action of glycine, to a large extent, reflects a block of fast desensitization, via an increase in the rate constant for return of desensitized NMDA receptors to their resting state. Drugs that competitively displace glycine from its binding site, but that are without glycine‐like activity, act as noncompetitive NMDA receptor antagonists. The combination of these unusual physiological and pharmacological properties seems to have been exploited in the brain to allow the NMDA receptor to gate a variety of complex behaviours, including memory formation, neuronal cell death in stroke and ischemia, and electrical excitability in epilepsy. The existence of multiple ligand‐binding sites on the NMDA receptor complex provides many potential avenues for the development of new classes of centrally active drugs.
Novel approach to studying N‐methyl‐D‐aspartate receptor function in the kindling model of epilepsy
Authors: McNamara James O. , Bonhaus Douglas W. , Nadler J. Victor 
Published: January 2005

AbstractKindling is the most widely studied animal model of epilepsy. This manuscript reviews studies of the role of N‐methyl‐D‐aspartate (NMDA) receptors in the kindling model. Pharmacologic studies suggest that 1) NMDA receptor activation contributes to the development of kindling; and 2) kindled seizures may be due in part to enhanced activation of NMDA receptors. Electrophysiologic studies demonstrate that NMDA receptors participate in synaptic activation of hippocampal dentate granule cells of kindled but not control animals. Biochemical studies demonstrate an enhanced sensitivity of kindled hippocampal slices to NMDA. Raising the possibility of enhanced function of the NMDA receptor channel complex itself. Radiohistochemical studies disclose no increase in affinity or number of NMDA receptors. Major emphasis is placed on development of a novel approach to study NMDA receptor function in isolated membrances, namely NMDA control of radiolabeled uncompetitive antagonist binding to a site presumably within the NMDA channel. Application of this novel approach will permit examination of NMDA and glycine receptor function and their control by zinc in the kindling model.