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  • 1
    Electronic Resource
    Electronic Resource
    Immobilization Decreases Amino Acid Concentrations in Plasma but Maintains or Increases Them in Brain (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 46 (1986), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Immobilization for 2 h significantly decreased plasma concentrations of 13 of 16 amino acids assayed, including the transmitter amine precursors tyrosine and total tryptophan. The level of plasma free tryptophan, however, was increased. Despite the reduced plasma levels, corresponding brain concentrations of many large neutral amino acids (LNAAs) were increased (tryptophan, phenylalanine, valine, leucine, and isoleucine). Brain concentrations of tyrosine and the other amino acids measured were unaltered. The results for the LNAAs were not explained by calculated brain influx rates. Therefore, altered influx kinetics or perhaps altered brain protein metabolism or efflux may be responsible. Comparison of calculated brain influxes and brain concentrations of LNAAs suggests that the rise in level of plasma free tryptophan during immobilization is not responsible for the increase in level of brain tryptophan and that the mechanism responsible for the maintenance of or increase in brain concentrations of the other LNAAs is probably involved. Maintenance of brain concentrations of basic amino acids is explicable by reduced competition for brain uptake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1986.tb12947.x
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  • 2
    Electronic Resource
    Electronic Resource
    Enhancement of Brain Dopamine Metabolism by Tyrosine During Immobilisation: An In Vivo Study Using Repeated Cerebrospinal Fluid Sampling in Conscious Rats (1987)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 48 (1987), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Central dopamine (DA) and 5-hydroxytrypta-mine (5-HT) metabolism was monitored in conscious, freely moving rats by determination of levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and ho-movanillic acid (HVA) and the 5-HT metabolite 5-hydroxy-indoleacetic acid (5-HIAA) in CSF samples withdrawn repeatedly from the cisterna magna and treated with acid to hydrolyse DOPAC and HVA conjugates. The effect of tyrosine on DA metabolism was investigated. Time courses of metabolite concentrations in individual rats in a quiet room showed that tyrosine (20, 50, or 200 mg/kg i.p.) was without significant effect; brain changes were essentially in agreement. However, the increases of CSF DOPAC and HVA levels that occurred on immobilisation for 2 h were further enhanced by tyrosine (200 mg/kg). The associated increases of 5-HIAA level were unaffected. The corresponding increases of DA metabolite concentrations in the brains of immobilised rats given tyrosine were less marked than the CSF changes and only reached significance for “rest of brain” DOPAC. The CSF studies revealed large interindividual variation in the magnitude and duration of the effects of immobilisation on transmitter amine metabolism. These results may help toward the elucidation of possible relationships between the neurochemical and behavioural effects of stress.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1987.tb05653.x
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  • 3
    Electronic Resource
    Electronic Resource
    Characteristics of Analgesias Induced by Brief or Prolonged Stress (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 467 (1986), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1986.tb14621.x
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  • 4
    Electronic Resource
    Electronic Resource
    Monitoring Dopamine Metabolism in the Brain of the Freely Moving Rat (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 473 (1986), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1986.tb23619.x
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  • 5
    Electronic Resource
    Electronic Resource
    The antiemetic drug trimethobenzamide prevents hypophagia due to acetyl salicylate, but not to 5-HT1B or 5-HT1C agonists (1988)
    Springer
    Psychopharmacology 96 (1988), S. 101-103 
    Details
    ISSN: 1432-2072
    Keywords: Antiemetics ; Trimethobenzamide ; Anorexia ; 5-HT1B agonists ; 5-HT1C agonists ; RU 24969 ; mCPP ; TFMPP ; Salicylate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pretreatment with the antiemetic agent trimethobenzamide (TMB) prevented the hypophagic response of rats to acetyl salicylate (a known emetic in man and dogs). However, it did not affect the hypophagic responses to the 5-HT1B agonist RU 24969, or to the 5-HT1C/5-HT1B agonistsmCPP and TFMPP. The results therefore suggest that the hypophagic effects of the 5-HT agonists do not involve a malaise-dependent mechanism similar to that mediating the effect of acetyl salicylate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02431540
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  • 6
    Electronic Resource
    Electronic Resource
    Evidence that hypophagia induced bymCPP and TFMPP requires 5-HT1C and 5-HT1B receptors; hypophagia induced by RU 24969 only requires 5-HT1B receptors (1988)
    Springer
    Psychopharmacology 96 (1988), S. 93-100 
    Details
    ISSN: 1432-2072
    Keywords: 5-HT1B and 5-HT1C receptors ; mCPP ; TFMPP ; RU 24969 ; Anorexia Food intake ; 5-HT antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Sprague-Dawley rats deprived of food for 18 h were injected with the 5-HT agonists RU 24969, 1-(3-chlorophenyl)piperazine (mCPP) or 1-[3-(trifluoromethyl)phenyl)]piperazine (TFMPP) and 20 min later presented with their normal diet. Food intake was determined 1, 2 and 4 h later. All three drugs reduced intake over 1 and 2 h. Three out of four drugs with high affinity for 5-HT1C receptors (metergoline, mianserin, and mesulergine but not cyproheptadine) opposed hypophagia caused bymCPP. Another drug reported to have high affinity for the 5-HT1C site, 1-naphthyl-piperazine (1-NP), also blocked the hypophagic response tomCPP at doses which attenuatedmCPP-induced hypolocomotion. Only one of the above drugs (metergoline) which also has high affinity for other 5-HT sites opposed hypophagia caused by RU 24969. Two out of three 5-HT1B receptor antagonists [(±) cyanopindolol, (−) propranolol, but not (−) pindolol)] which oppose hypophagia caused by RU 24969 (Kennett et al. 1987) also opposed hypophagia caused bymCPP. The 5-HT2 antagonists ketanserin and ritanserin, the 5-HT3 antagonist ICS 205-930 and the α2 adrenoceptor antagonist idazoxan did not oppose the hypophagic effect ofmCPP. In agreement with results formCPP, hypophagia caused by TFMPP was opposed by both, mianserin and (±) cyanopindolol. Given alone, mianserin 1-NP and cyproheptadine but not ICS 205-930 increased food consumption of normally fed rats. The results suggest that RU 24969-induced hypophagia depends on 5-HT1B receptors but not on 5-HT1C receptors, whilemCPP (and TFMPP)-induced hypophagia may depend on both receptors. Thus, 5-HT1C and 5-HT1B receptors may evoke hypophagia via a common pathway but the effect of antagonists implies that at the doses usedmCPP and TFMPP act predominantly at 5-HT1C receptors. Since only the hypophagic response tomCPP is blocked by cyanopindolol and (−) propranolol (Kennett and Curzon 1988) it is unlikely to be secondary to hypoactivity induced by the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02431539
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  • 7
    Electronic Resource
    Electronic Resource
    5-HT1C receptor antagonists have anxiolytic-like actions in the rat social interaction model (1992)
    Springer
    Psychopharmacology 107 (1992), S. 379-384 
    Details
    ISSN: 1432-2072
    Keywords: Anxiety ; 5-HT ; 5-HT1C receptors ; Social interaction ; Mianserin ; Benzodiazepines ; Ketanserin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of a range of 5-HT receptor antagonists were examined in an animal model of anxiety — the social interaction test. Six antagonists with high affinity for 5-HT1C receptors; mianserin, (+) mianserin, 1-naphthyl piperazine, ICI 169 369, pizotifen and LY 53857 all increased the time spent in active social interaction by pairs of weight-matched rats under high light unfamiliar conditions. As locomotion was only increased by 1-NP and then only at high doses, the effect of the drugs is consistent with anxiolysis. These properties were shared by the benzodiazepine anxiolytic chlordiazepoxide but not by the specific 5-HT2 antagonists ketanserin and altanserin, nor by the 5-HT1A and 5-HT1B antagonists cyanopindolol and pindolol. Similarly, neither the adrenergic α2 antagonist idazoxan, the α2 antagonist and putative 5-HT1D partial agonist yohimbine nor the H1 antagonist mepyramine had any significant effect. Since (+)mianserin, LY 53857 and ICI 169 369 at least have low affinity for 5-HT3 receptors these receptors are also unlikely to be involved. The results therefore imply that the observed anxiolytic effects of the drugs are likely to be mediated by 5-HT1C receptor blockade.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245165
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  • 8
    Electronic Resource
    Electronic Resource
    Evidence that 5-HT2C receptor antagonists are anxiolytic in the rat Geller-Seifter model of anxiety (1994)
    Springer
    Psychopharmacology 114 (1994), S. 90-96 
    Details
    ISSN: 1432-2072
    Keywords: 5-HT1C receptors ; 5-HT2 receptors ; 5-HT2B receptors ; 5-HT ; Anxiety ; Geller-Seifter test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Four non-selective 5-HT2C/5-HT2A receptor antagonists, mianserin (2–8 mg/kg), 1-naphthyl piperazine (1-NP) (0.5–1 mg/kg), ICI 169,369 (20 mg/kg) and LY 53857 (5 mg/kg), increased punished responding for a food reward in the rat Geller-Seifter test 30 min after subcutaneous (SC) administration. This property was shared by the benzodiazepine anxiolytic chlordiazepoxide (5 mg/kg SC). However, the selective 5-HT2A receptor antagonists ketanserin (0.2–1 mg/kg SC) and altanserin (0.5, 1 mg/kg SC) had little effect. The 5-HT1A, 5-HT1B andβ-adrenergic receptor antagonists pindolol and cyanopindolol (6 mg/kg SC) did not affect punished responding either, nor did the 5-HT1D receptor partial agonist andα 2 adrenergic receptor antagonist yohimbine (2.5 mg/kg SC) or the histamine H1 receptor antagonist mepyramine (1 mg/kg SC). Unpunished responding was also modestly increased after some doses of the 5-HT2C/5-HT2A receptor antagonists. However, this effect was inconsistent and was also seen after chlordiazepoxide. Furthermore, it was not associated with the increase in punished responding observed in rats orally treated with mianserin (10, 20 mg/kg), 1-NP (10, 20 mg/kg) or ICI 169,369 (50 mg/kg). The action of the 5-HT2C/5-HT2A receptor antagonists tested is therefore consistent with anxiolysis. The results also strongly suggest that this effect is mediated by blockade of the 5-HT2C receptor, although the possibility of 5-HT2B receptor mediation is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245448
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  • 9
    Electronic Resource
    Electronic Resource
    BRL 46470A: a highly potent, selective and long acting 5-HT3 receptor antagonist with anxiolytic-like properties (1993)
    Springer
    Psychopharmacology 110 (1993), S. 257-264 
    Details
    ISSN: 1432-2072
    Keywords: Anxiolytic ; 5-HT3 receptors ; Social interaction ; X-maze ; Bezold-Jarisch reflex ; BRL 46470A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The novel 5-HT3 antagonist, BRL 46470A (endo-N-(8-methyl-8-azabicyclo [3.2.1]oct-3-yl)2,3-dihydro-3,3 dimethyl-indole-1-carboxamide, hydrochloride), has been investigated in a series of in vitro and in vivo tests, including the effect of the drug in models of anxiolysis. In classical tests for 5-HT3 receptor antagonism, BRL 46470A was shown to antagonise 5-HT3 mediated responses in the guinea-pig ileum [pA2 8.3±0.5, slope 0.98±0.20, mean±SEM (5)], the rabbit isolated heart (pA2 10.1±0.1, slope 1.2±0.2,n=5) and the rat Bezold-Jarisch model (ID50 0.7 µg/kg IV±0.1,n=8), with a long duration of action (〉3 h). BRL 46470A selectively displaced [3H]-BRL 43694 from 5-HT3 binding sites in rat brain membranes (Ki 0.32 nM±0.04,n=4) without displacing (at concentrations greater than 1 µM) a wide variety of ligands binding to other neurotransmitter receptors, opioid receptors and to neurotransmitter gated ion channel complexes. In vivo, BRL 46470A showed anxiolytic-like activity in two animal models predictive of antianxiety effects-elevated X-maze and social interaction in rats. In both models, BRL 46470A showed significant activity over a wide dose-range following both oral (0.0001–0.1 mg/kg PO) and systemic administration. The unique level of potency of BRL 46470A was apparent in the rat social interaction test and was shown to be 100 fold more potent than the 5-HT3 receptor antagonist ondansetron, with no evidence of a bell-shaped dose response curve over 4 orders of magnitude. BRL 46470A (0.0001 and 0.01 mg/kg SC) also reduced the anxiogenic effects of m-CPP (1-(3-chlorophenyl) piperazine) in the rat elevated X-maze. BRL 46470A is therefore a chemically novel potent and selective 5-HT3 receptor antagonist with anxiolytic potential and a long duration of action in animal studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02251279
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  • 10
    Electronic Resource
    Electronic Resource
    Effect of SB 200646A, a 5-HT2C/5-HT2B receptor antagonist, in two conflict models of anxiety (1995)
    Springer
    Psychopharmacology 118 (1995), S. 178-182 
    Details
    ISSN: 1432-2072
    Keywords: SB 200646A ; 5-HT2C ; 5-HT2B ; Anxiety ; Conflict models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract SB 200646A is the first selective 5-HT2C/5-HT2B receptor antagonist and has previously been observed to have anxiolytic-like properties in the rat social interaction test. In the present study the effects of the compound in two conflict models of anxiety, the rat Geller-Seifter and marmoset conflict test, were examined. In the rat Geller-Seifter test, suppressed responding was increased by all doses of SB 200646A between 5 and 40 mg/kg PO when given 1 h pretest. Unsuppressed responding was slightly increased only at 10 mg/kg PO. Suppressed responding was also increased by the benzodiazepine anxiolytic, chlordiazepoxide, at 1, 2.5 and 5 mg/kg PO 1 h pretest. Unsuppressed responding was modestly increased by chlordiazepoxide only at 5 mg/kg PO. In the marmoset conflict test marmosets were trained to lever press for a palatable food reward. Lever pressing was subsequently suppressed by air puffs. In this procedure suppressed responding was increased by both the benzodiazepine anxiolytic diazepam at 2 and 5 mg/kg PO and SB 200646A after 10 and 20 mg/kg PO. Both treatments caused small increases in unsuppressed responding at 2 and 20 mg/kg PO respectively. Taken together with the previous effects of SB 200646A in the rat social interaction test, this is compelling evidence that 5-HT2C/2B receptor antagonists may possess anxiolytic properties.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245837
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