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Author (up) Andersson, D.R.; Bjornsson, E.; Bergquist, F.; Nissbrandt, H.
Title Motor activity-induced dopamine release in the substantia nigra is regulated by muscarinic receptors Type Journal Article
Year 2010 Publication Experimental Neurology Abbreviated Journal Exp Neurol
Volume 221 Issue 1 Pages 251-259
Keywords Analysis of Variance; Animals; Area Under Curve; Brain Injuries/chemically induced/*pathology; Chromatography, High Pressure Liquid/methods; Dendrites/drug effects/metabolism; Disease Models, Animal; Dopamine/*metabolism; Dose-Response Relationship, Drug; Electrochemistry/methods; Female; Functional Laterality; Mecamylamine/pharmacology; Microdialysis/methods; Motor Activity/drug effects/*physiology; Muscarinic Antagonists/pharmacology; Nicotinic Antagonists/pharmacology; Oxidopamine; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic/*physiology; Rotarod Performance Test/methods; Scopolamine Hydrobromide/pharmacology; Substantia Nigra/drug effects/*metabolism/pathology; gamma-Aminobutyric Acid/metabolism
Abstract Nigro-striatal neurons release dopamine not only from their axon terminals in the striatum, but also from somata and dendrites in the substantia nigra. Somatodendritic dopamine release in the substantia nigra can facilitate motor function by mechanisms that may act independently of axon terminal dopamine release in the striatum. The dopamine neurons in the substantia nigra receive a cholinergic input from the pedunculopontine nucleus. Despite recent efforts to introduce this nucleus as a potential target for deep brain stimulation to treat motor symptoms in Parkinson's disease; and the well-known antiparkinsonian effects of anticholinergic drugs; the cholinergic influence on somatodendritic dopamine release is not well understood. The aim of this study was to investigate the possible regulation of locomotor-induced dopamine release in the substantia nigra by endogenous acetylcholine release. In intact and 6-OHDA hemi-lesioned animals alike, the muscarinic antagonist scopolamine, when perfused in the substantia nigra, amplified the locomotor-induced somatodendritic dopamine release to approximately 200% of baseline, compared to 120-130% of baseline in vehicle-treated animals. A functional importance of nigral muscarinic receptor activation was demonstrated in hemi-lesioned animals, where motor performance was significantly improved by scopolamine to 82% of pre-lesion performance, as compared to 56% in vehicle-treated controls. The results indicate that muscarinic activity in the substantia nigra is of functional importance in an animal Parkinson's disease model, and strengthen the notion that nigral dopaminergic regulation of motor activity/performance is independent of striatal dopamine release.
Call Number Serial 308
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Author (up) Arias-Carrion, O.; Palomero-Rivero, M.; Millan-Aldaco, D.; Haro, R.; Drucker-Colin, R.; Murillo-Rodriguez, E.
Title Infusion of modafinil into anterior hypothalamus or pedunculopontine tegmental nucleus at different time-points enhances waking and blocks the expression of recovery sleep in rats after sleep deprivation Type Journal Article
Year 2011 Publication Experimental Neurology Abbreviated Journal Exp Neurol
Volume 229 Issue 2 Pages 358-363
Keywords Analysis of Variance; Animals; Benzhydryl Compounds/pharmacology/*therapeutic use; Central Nervous System Stimulants/pharmacology/*therapeutic use; Electroencephalography; Hypothalamus, Anterior/*drug effects; Microinjections; Pedunculopontine Tegmental Nucleus/*drug effects; Rats; Sleep/*drug effects; Sleep Deprivation/*drug therapy; Wakefulness/*drug effects
Abstract Clinical studies have indicated that the primary pharmacological activity of modafinil (MOD) is inducing wakefulness; however, the brain targets that underlie its wake-promoting activity have not been described. In the present study, we show that MOD injected into sleep-wake related brain areas promoted alertness. If administered (10, 20, or 30 mug/1 muL) into either anterior hypothalamus (AH) or pedunculopontine tegmental nucleus (PPTg) at 08:00, 12:00 or 16:00 h, MOD enhanced wakefulness whereas diminished slow wave sleep as well as rapid eye movement sleep. In addition, microinjection of MOD (10, 20, or 30 mug/1 muL) either into AH or PPTg after total sleep deprivation prevented the sleep rebound. Taken together, these observations suggest that AH and PPTg play a key role in the wake-inducing effects of MOD and encourage further experimentation to draw a possible mechanism of action.
Call Number Serial 330
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Author (up) Arolfo, M.P.; Brioni, J.D.
Title Diazepam impairs place learning in the Morris water maze Type Journal Article
Year 1991 Publication Behavioral and Neural Biology Abbreviated Journal Behav Neural Biol
Volume 55 Issue 1 Pages 131-136
Keywords Animals; Diazepam/*pharmacology; Discrimination Learning/*drug effects; Dose-Response Relationship, Drug; Escape Reaction/*drug effects; Male; Mental Recall/drug effects; Orientation/*drug effects; Rats; Rats, Inbred Strains; Reaction Time/drug effects; Retention (Psychology)/*drug effects
Abstract The effect of diazepam (0.3, 1.0, and 3.0 mg/kg) on the acquisition and retention of place learning was evaluated. The analysis of escape latencies indicates that 1.0 and 3.0 mg/kg diazepam significantly impaired the retention of spatial information. When a free swim trial was carried out only control animals showed spatial bias to the target quadrant. The absence of spatial bias in the group that received 0.3 mg/kg suggests that the amnesic effect of diazepam can be seen at doses similar to or even lower than the anxiolytic ones, and that the GABA/benzodiazepine receptor complex is highly sensitive to the cognitive impairment induced by diazepam in spatial tasks.
Call Number Serial 249
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Author (up) Arrant, A.E.; Schramm-Sapyta, N.L.; Kuhn, C.M.
Title Use of the light/dark test for anxiety in adult and adolescent male rats Type Journal Article
Year 2013 Publication Behavioural Brain Research Abbreviated Journal Behav Brain Res
Volume 256 Issue Pages 119-127
Keywords Adrenergic alpha-2 Receptor Antagonists/pharmacology; Age Factors; Animals; Antidepressive Agents/pharmacology; Anxiety/*diagnosis/drug therapy; Carbolines/pharmacology; Exploratory Behavior/drug effects; Factor Analysis, Statistical; *Light; Male; Motor Activity/drug effects; *Neuropsychological Tests; Rats, Sprague-Dawley; Regression Analysis; Risk-Taking; Time Factors; Yohimbine/pharmacology; Adolescence; Anxiety; Fg-7142; Factor analysis; Light/dark test; Yohimbine
Abstract The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28-34) and adult (PN67-74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) and the alpha(2) adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence.
Call Number Serial 1614
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Author (up) Atherton, P.J.; Babraj, J.; Smith, K.; Singh, J.; Rennie, M.J.; Wackerhage, H.
Title Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation Type Journal Article
Year 2005 Publication FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology Abbreviated Journal Faseb J
Volume 19 Issue 7 Pages 786-788
Keywords Adaptation, Physiological; Adenylate Kinase/*metabolism; Animals; Electric Stimulation; Enzyme Activation; Male; Mitogen-Activated Protein Kinases/metabolism; Muscle Contraction; Muscle Proteins/biosynthesis; Muscle, Skeletal/*physiology; Myofibrils/metabolism; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phosphorylation; Physical Conditioning, Animal; Physical Endurance/physiology; Physical Exertion; Protein Kinases/*metabolism; Proto-Oncogene Proteins c-akt/*metabolism; RNA-Binding Proteins/*metabolism; Rats; Rats, Wistar; Sarcoplasmic Reticulum/metabolism; Signal Transduction; TOR Serine-Threonine Kinases; Transcription Factors/*metabolism; Tumor Suppressor Proteins/*metabolism
Abstract Endurance training induces a partial fast-to-slow muscle phenotype transformation and mitochondrial biogenesis but no growth. In contrast, resistance training mainly stimulates muscle protein synthesis resulting in hypertrophy. The aim of this study was to identify signaling events that may mediate the specific adaptations to these types of exercise. Isolated rat muscles were electrically stimulated with either high frequency (HFS; 6x10 repetitions of 3 s-bursts at 100 Hz to mimic resistance training) or low frequency (LFS; 3 h at 10 Hz to mimic endurance training). HFS significantly increased myofibrillar and sarcoplasmic protein synthesis 3 h after stimulation 5.3- and 2.7-fold, respectively. LFS had no significant effect on protein synthesis 3 h after stimulation but increased UCP3 mRNA 11.7-fold, whereas HFS had no significant effect on UCP3 mRNA. Only LFS increased AMPK phosphorylation significantly at Thr172 by approximately 2-fold and increased PGC-1alpha protein to 1.3 times of control. LFS had no effect on PKB phosphorylation but reduced TSC2 phosphorylation at Thr1462 and deactivated translational regulators. In contrast, HFS acutely increased phosphorylation of PKB at Ser473 5.3-fold and the phosphorylation of TSC2, mTOR, GSK-3beta at PKB-sensitive sites. HFS also caused a prolonged activation of the translational regulators p70 S6k, 4E-BP1, eIF-2B, and eEF2. These data suggest that a specific signaling response to LFS is a specific activation of the AMPK-PGC-1alpha signaling pathway which may explain some endurance training adaptations. HFS selectively activates the PKB-TSC2-mTOR cascade causing a prolonged activation of translational regulators, which is consistent with increased protein synthesis and muscle growth. We term this behavior the “AMPK-PKB switch.” We hypothesize that the AMPK-PKB switch is a mechanism that partially mediates specific adaptations to endurance and resistance training, respectively.
Call Number Serial 2075
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Author (up) Bayer, L.; Eggermann, E.; Serafin, M.; Grivel, J.; Machard, D.; Muhlethaler, M.; Jones, B.E.
Title Opposite effects of noradrenaline and acetylcholine upon hypocretin/orexin versus melanin concentrating hormone neurons in rat hypothalamic slices Type Journal Article
Year 2005 Publication Neuroscience Abbreviated Journal Neuroscience
Volume 130 Issue 4 Pages 807-811
Keywords Acetylcholine/pharmacology/*physiology; Action Potentials/drug effects/physiology; Animals; Arousal/drug effects/physiology; Cholinergic Agonists/pharmacology; Hypothalamic Area, Lateral/cytology/drug effects/*metabolism; Hypothalamic Hormones/*metabolism; Intracellular Signaling Peptides and Proteins/*metabolism; Locus Coeruleus/physiology; Melanins/*metabolism; Models, Neurological; Neural Inhibition/drug effects/physiology; Neural Pathways/cytology/drug effects/metabolism; Neurons/drug effects/*metabolism; Neuropeptides/*metabolism; Norepinephrine/pharmacology/*physiology; Organ Culture Techniques; Patch-Clamp Techniques; Pedunculopontine Tegmental Nucleus/physiology; Pituitary Hormones/*metabolism; Rats; Rats, Sprague-Dawley; Sleep/physiology; Synaptic Transmission/drug effects/physiology
Abstract Hypocretin/orexin (Hcrt/Orx) and melanin concentrating hormone (MCH) are peptides contained in overlapping cell groups of the lateral hypothalamus and commonly involved in regulating sleep-wake states and energy balance, though likely in different ways. To see if these neurons are similarly or differentially modulated by neurotransmitters of the major brainstem arousal systems, the effects of noradrenaline (NA) and carbachol, a cholinergic agonist, were examined on identified Hcrt/Orx and MCH neurons in rat hypothalamic slices. Whereas both agonists depolarized and excited Hcrt/Orx neurons, they both hyperpolarized MCH neurons by direct postsynaptic actions. According to the activity profiles of the noradrenergic locus coeruleus and cholinergic pontomesencephalic neurons across the sleep-waking cycle, the Hcrt/Orx neurons would be excited by NA and acetylcholine (ACh) and thus active during arousal, whereas the MCH neurons would be inhibited by NA and ACh and thus inactive during arousal while disinhibited and possibly active during slow wave sleep. According to the present pharmacological results, Hcrt/Orx neurons may thus stimulate arousal in tandem with other arousal systems, whereas MCH neurons may function in opposition with other arousal systems and thus potentially dampen arousal to promote sleep.
Call Number Serial 331
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Author (up) Berger, U.V.; Carter, R.E.; Coyle, J.T.
Title The immunocytochemical localization of N-acetylaspartyl glutamate, its hydrolysing enzyme NAALADase, and the NMDAR-1 receptor at a vertebrate neuromuscular junction Type Journal Article
Year 1995 Publication Neuroscience Abbreviated Journal Neuroscience
Volume 64 Issue 4 Pages 847-850
Keywords Animals; Dipeptidases/*immunology/physiology; Dipeptides/*immunology/physiology; Glutamate Carboxypeptidase II; Immunohistochemistry; Neuromuscular Junction/*physiology; Phrenic Nerve; Rats; Receptors, N-Methyl-D-Aspartate/*immunology/physiology; Vertebrates
Abstract Although glutamate is thought to be the neurotransmitter at the invertebrate neuromuscular junction, acetylcholine is accepted as the primary neurotransmitter of the vertebrate motoneurons. N-acetylaspartylglutamate, a dipeptide localized in putative glutamatergic neurons in brain, is also found in high concentrations (> mM) in mammalian motoneurons and the ventral roots of spinal cord. N-acetylaspartylglutamate, which is released from neurons by depolarization in a Ca(2+)-dependent fashion, is implicated in glutamatergic transmission in two ways: it is a partial agonist at NMDA receptors, and it is cleaved to yield extracellular glutamate and N-acetylasparate by the specific peptidase N-acetylated alpha-linked acidic dipeptidase. Given the localization of N-acetylaspartylglutamate in motor neuronal perikarya and axons, we wondered whether N-acetylaspartylglutamate or glutamate cleaved from N-acetylaspartylglutamate by N-acetylated alpha-linked acidic dipeptidase may also play a role in neuromuscular transmission. Here we describe the immunocytochemical detection at the rat neuromuscular junction of N-acetylaspartylglutamate in terminals of motoneurons, of N-acetylated alpha-linked acidic dipeptidase in perisynaptic Schwann cells, and of the NMDAR-1 glutamate receptor subunit on postsynaptic muscle membranes. These results point to a potential role for N-acetylaspartylglutamate at the rat neuromuscular junction. Further, this is the first demonstration of a glutamate receptor protein at vertebrate neuromuscular synapses. Together with other recent findings, our results suggest that glutamate-like molecules are involved in neuromuscular transmission not only in invertebrates but also in veretebrates where they may modulate signaling by acetylcholine.
Call Number Serial 114
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Author (up) Bhattacharya, S.K.; Satyan, K.S.; Chakrabarti, A.
Title Anxiogenic action of caffeine: an experimental study in rats Type Journal Article
Year 1997 Publication Journal of Psychopharmacology (Oxford, England) Abbreviated Journal J Psychopharmacol
Volume 11 Issue 3 Pages 219-224
Keywords Animals; Anxiety/*chemically induced; Caffeine/antagonists & inhibitors/*pharmacology; Central Nervous System Stimulants/*pharmacology; Drug Tolerance; Exploratory Behavior/*drug effects; Male; Phosphodiesterase Inhibitors/*pharmacology; Rats; Rats, Wistar; Social Behavior; Substance Withdrawal Syndrome; Yohimbine/antagonists & inhibitors/pharmacology
Abstract The anxiogenic action of caffeine (10, 25 and 50 mg/kg, i.p.) was investigated in rats and compared with that of yohimbine (2 mg/kg, i.p.). The experimental methods used were the open-field, elevated plus-maze, social interaction and novelty-suppressed feeding latency tests. Caffeine produced a dose-related profile of behavioural changes, which were qualitatively similar to those induced by yohimbine and which indicate an anxiogenic activity in rodents. Thus, both the drugs reduced ambulation and rears, and increased immobility and defaecation in the open-field test. They decreased the number of entries and time spent on the open arms of the elevated-plus maze, reduced social interaction in paired rats and increased the feeding latency in an unfamiliar environment in 48-h food-deprived rats. Lorazepam, a well known benzodiazepine anxiolytic agent, attenuated the anxiogenic effects of caffeine and yohimbine. Subchronic administration of caffeine (50 mg/kg, i.p.) for 21 days, in different groups of animals, induced a significant degree of tolerance in the elevated plus-maze test, which was statistically significant after 14 and 21 days' treatment. Yohimbine, however, did not induce similar tolerance. When caffeine (50 mg/kg, i.p.) was withdrawn after 21 days' administration, to a separate group of rats, significant withdrawal anxiety was observed 48 h later as noted in the elevated plus-maze test. The investigations support clinical evidence of caffeine-induced anxiety, tolerance to anxiety on continued use, and withdrawal anxiety in chronic caffeine-containing beverage users.
Call Number Serial 1531
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Author (up) Bienkowski, P.; Kostowski, W.
Title Discrimination of ethanol in rats: effects of nicotine, diazepam, CGP 40116, and 1-(m-chlorophenyl)-biguanide Type Journal Article
Year 1998 Publication Pharmacology, Biochemistry, and Behavior Abbreviated Journal Pharmacol Biochem Behav
Volume 60 Issue 1 Pages 61-69
Keywords 2-Amino-5-phosphonovalerate/administration & dosage/*analogs & derivatives/pharmacology; Animals; Biguanides/administration & dosage/*pharmacology; Diazepam/administration & dosage/*pharmacology; Discrimination Learning/*drug effects/physiology; Drug Interactions; Ethanol/*pharmacology; GABA Modulators/administration & dosage/pharmacology; Male; Nicotine/administration & dosage/*pharmacology; Nicotinic Agonists/administration & dosage/pharmacology; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors; Reinforcement Schedule; Serotonin Receptor Agonists/administration & dosage/pharmacology
Abstract The drug discrimination paradigm was used to evaluate the role of certain ligand-gated ion channels in the discriminative stimulus properties of ethanol. Rats were trained to discriminate ethanol (1.0 g/kg) from saline vehicle under the FR10 schedule of sweetened milk reinforcement. The discrimination of lower ethanol doses was enhanced by either the GABA(A) receptor positive modulator, diazepam (0.5 mg/kg), or nicotinic acetylcholine receptor agonist, nicotine (0.3 mg/kg). Neither diazepam nor nicotine produced any effect on the rate of responding. Both the NMDA receptor competitive antagonist, CGP 40116 (0.5 mg/kg) and the 5-HT) receptor agonist, 1-(m-chlorophenyl)-biguanide (5.0 mg/kg) enhanced the cueing properties of lower ethanol doses, but these effects were associated with a significant reduction in the response rate. The ethanol-like stimulus effects produced by diazepam or CGP 40116 were not influenced by 0.3 mg/kg nicotine. In contrast, CGP 40116 moderately enhanced the ethanol-like stimulus effects of diazepam. The present results show that: 1) pretreatment with nicotine, diazepam, CGP 40116 or 1-(m-chlorophenyl)-biguanide enhance the ethanol discrimination; 2) neither the GABA(A) nor the NMDA receptor complex alone is critically involved in the nicotine-induced enhancement of the ethanol discrimination; 3) NMDA receptor competitive antagonist and GABAergic benzodiazepine derivative may produce moderate additive effects in rats trained to discriminate ethanol.
Call Number Serial 1329
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Author (up) Bignami, A.; Eng, L.F.; Dahl, D.; Uyeda, C.T.
Title Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence Type Journal Article
Year 1972 Publication Brain Research Abbreviated Journal Brain Res
Volume 43 Issue 2 Pages 429-435
Keywords Animals; Antibodies; Antibody Formation; Brain/*pathology; *Brain Chemistry; Cerebellum/immunology; Cross Reactions; Dementia/pathology; Dogs/immunology; *Fluorescent Antibody Technique; Gliosis/pathology; Guinea Pigs/immunology; Humans; Immune Sera; Male; Medulla Oblongata/immunology; Middle Aged; *Nerve Tissue Proteins; *Neuroglia; Optic Nerve/immunology; Rabbits/immunology; Rats/immunology
Abstract The glial fibrillary acidic (GFA) protein, a brain specific protein extracted from severely gliosed human tissue, is not species specific; cross-reaction occurs between anti-human GFA protein antibodies and brain extracts of rabbit, guinea pig, rat and dog. Using anti-GFA protein antiserum, astrocytes are selectively stained with the indirect immunofluorescence technique in both normal and pathological (gliosed) brain tissue.
Call Number Serial 113
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