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  • 1
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 553 (1989), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 553 (1989), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 59 (1992), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) was measured in selected regions of the cervical, thoracic, and lumbar spinal cord of untreated rabbits and, following intrathecal injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), in the thoracolumbar cord in rats using a sheep antiserum raised against tyrosine0 calcitonin gene-related peptide28-37. In the cervical, thoracic, and lumbar segments of the rabbit spinal cord, CGRP-LI levels were 15–50-fold higher in the dorsal than in the ventral grey region in the same segment. The only segmental variation in CGRP-LI levels was in the dorsal white region, where levels in the thoracic cord were lower than those in cervical or lumbar segments. Within individual spinal segments, the pattern of distribution of CGRP-LI in the rabbit spinal cord was analogous to that in other species previously examined, including rat, human, and cat spinal cord. Intrathecal injection of 5,7-DHT, which caused 85–91% depletion of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid from the thoracolumbar ventral spinal cord, did not affect choline acetyltransferase activity, which is colocalized with CGRP in motoneurones in this spinal cord region. In contrast, intrathecal 5,7-DHT produced a threefold increase in CGRP-LI in the ventral thoracolumbar cord, suggesting that spinal motoneurones selectively increase production of CGRP 10 days after neurotoxin-induced denervation of bulbospinal raphe neuronal input.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 48 (1987), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The distribution of thyrotrophin-releasing hormone (TRH), substance P, and the indoleamines [5-hy-droxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)] has been examined in selected regions of the thoracic and lumbar spinal cord of the rabbit using sensitive radioimmunoassays for the first two and HPLC with electrochemical detection for the indoleamines. The levels of TRH- and substance P-like immunoreactivity (TRH-I and SP-I, respectively) were greatest in the ventral and dorsal grey matter, respectively. The level of TRH-I in most thoracic regions was greater than that in equivalent lumbar regions, but the only segmental difference in SP-I was in the ventral grey matter, where the lumbar segment contained more immunoreactivity. 5-HT and 5-HIAA were more evenly distributed than either peptide and showed no segmental variation in levels in equivalent regions, but the ventral grey matter contained significantly higher levels of 5-HT and had a greater 5-HT/5-HIAA ratio than all other regions. The absolute levels and the overall distribution of SP-I, TRH-I, and indoleamines in the thoracolumbar cord of the rabbit was very similar to that previously reported in both rats and humans, and the possible functional role of the peptides and indoleamines in spinal neurones is discussed.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The antinociceptive effects of Δ9-tetrahydrocannabinol (Δ9-THC) have been widely described; however, its therapeutic potential may be limited by secondary effects. We investigated whether coadministration of low doses of cannabinoids or cannabinoids and morphine produced antinociception in the absence of side-effects. Effects of preadministration (i.p.) of Δ9-THC (1 or 2.5 mg/kg), cannabidiol (5 mg/kg), morphine (2 mg/kg), Δ9-THC + morphine, Δ9-THC + cannabidiol or vehicle on formalin-evoked nociceptive behaviour were studied over 60 min. Trunk blood and brains were collected 60 min after formalin injection and assayed for corticosterone and tissue levels of monoamines and metabolites, respectively. Drug effects on locomotor activity, core body temperature and grooming were assessed. Δ9-THC reduced both phases of formalin-evoked nociceptive behaviour, enhanced the formalin-evoked corticosterone response and increased the 4-hydroxy-3-methoxyphenylglycol : noradrenaline ratio in the hypothalamus. Cannabidiol alone had no effect on these indices and did not modulate the effects of Δ9-THC. Morphine reduced both phases of formalin-evoked nociceptive behaviour. Coadministration of Δ9-THC and morphine reduced the second phase of formalin-evoked nociceptive behaviour to a greater extent than either drug alone, and increased levels of thalamic 5-hydroxytryptamine. While the antinociceptive effects of Δ9-THC and morphine alone occurred at doses devoid of effects on locomotor activity, coadministration of Δ9-THC and morphine inhibited locomotor activity. In conclusion, coadministration of a low dose of morphine, but not cannabidiol, with Δ9-THC, increased antinociception and 5-hydroxytryptamine levels in the thalamus in a model of persistent nociception. Nevertheless, these enhanced antinociceptive effects were associated with increased secondary effects on locomotor activity.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effect of a 5-hydroxytryptamine7 (5-HT7) receptor-directed antisense oligonucleotide on rat behaviour and neuroendocrine function was investigated. Six days of intracerebroventricular 5-HT7 antisense oligonucleotide treatment significantly reduced [3H]5-HT binding to hypothalamic 5-HT7 receptors, whereas cortical 5-HT2C density remained unchanged. In rats on a food-restricted diet, both antisense and mismatch oligonucleotides reduced food intake and body weight compared with that in vehicle-treated controls by day 4 of administration. 5-HT7 antisense oligonucleotide administration did not affect exploratory or locomotor activity in photocell activity monitors on day 4 or elevated plus-maze behaviour on day 6 of intracerebroventricular treatment. 5-HT7 antisense oligonucleotide did not affect plasma corticosterone or prolactin levels or 5-HT turnover in either 5-HT cell body or terminal areas. These data demonstrate that intracerebroventricular 5-HT7 antisense oligonucleotide administration selectively reduced rat hypothalamic 5-HT7 receptor density without affecting any of the biochemical or behavioural measures. The results suggest that this antisense protocol could be a valuable tool to investigate central 5-HT7 receptor functions, and that this receptor is not critical for the control of neuroendocrine function or food intake.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The Siberian hamster provides a physiological model for understanding the hypothalamic control of energy metabolism as it undergoes annual photoperiod-regulated cycles of body weight (i.e. fattening in summer, and catabolism of fat stores in winter). As a first step to investigate whether enhanced serotonergic (5-HT) tone might underlie the catabolic processes in short days, we investigated whether serotonergic stimulation can produce catabolic actions in fat hamsters housed in long days. Acute treatment with the serotonin reuptake inhibitor (+/–) fenfluramine (8 mg/kg, i.p.) produced a prolonged, dose-dependent reduction in food intake in both photoperiods. Behavioural observations and radiotelemetry analyses revealed that this anorectic effect of fenfluramine was associated with short-term increases in locomotor activity and in core body temperature. In a subsequent series of studies, hamsters were pretreated with the 5-HT2C receptor antagonist SB242084 (4 mg/kg, i.p.). This 5-HT2C receptor antagonist completely blocked the anorectic actions of fenfluramine, but did not decrease the hyperthermia or hyperlocomotion induced by fenfluramine; thus, the anorectic actions of fenfluramine probably reflect actions via the 5-HT2C receptor. Consistent with these observations, treatment of hamsters with the 5-HT2C receptor agonist VER 3323 (10 mg/kg, i.p.) or the 5-HT1B/2C receptor agonist mCPP (3 mg/kg, i.p.) reduced food intake. The response to manipulation of serotonergic pathways was not affected by the ambient photoperiod in any of these studies. We conclude that the anorectic actions of fenfluramine are not an indirect consequence of serotonergic actions on arousal pathways, and that its actions on feeding in the Siberian hamster are most likely to be mediated by the 5-HT2C receptor.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Many studies point to an involvement of deficits in the serotonergic nervous system and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis function with depression. Indeed early life stress, involving HPA axis activation, may predispose susceptible individuals to develop depression in later life. This study investigates the effects of elevating the neuroendocrine stress hormone, corticosterone, for 1 week in adolescent rats on markers of serotonergic neurone function at adulthood. Slow release corticosterone pellets were implanted for 7 days and various serotonergic parameters, as well as plasma corticosterone levels, were measured on day 7 or on day 28 (21 days following removal of the pellet). The corticosterone implant attenuated weight gain and reduced adrenal weights compared to that in control rats implanted with a cholesterol pellet. After 7 days, with the implant still in place, the diurnal variation in plasma corticosterone was reduced so that the level was approximately at that of the evening peak throughout the day. Twenty-one days after removal of the implant, the diurnal variation in plasma corticosterone returned. Corticosterone treatment decreased [3H] 8-hydroxy-2-(di-n-propylamino)tetralin binding to the 5-hydroxytryptamine1A receptor in the cortex but not in the hippocampus. Corticosterone treatment also enhanced the circadian rhythm observed in 5-hydroxyindoleacetic acid level and the ratio of 5-hydroxyindoleacetic acid to the 5-hydroxytryptamine in the frontal cortex. Despite corticosterone pellet removal 21 days earlier, there was a persistent decrease in whole body and adrenal weight, cortical 5-hydroxytryptamine1A receptor binding and an alteration in the diurnal variation in the 5-hydroxytryptamine ‘turnover’ in the frontal cortex.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine2C receptors ; Social isolation ; Elevated plus-maze ; Anxiety ; Corticosterone ; Serotonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate whether isolation rearing alters 5-hydroxytryptamine2C (5-HT2C) receptors, the effect of the serotonin agonistm-chlorophenylpiperazine (mCPP) was examined on elevated plus-maze behaviour, plasma corticosterone and brain 5-HT2C receptor protein levels in rats. There was no distinction between behaviour or corticosterone levels in drug-free isolates or socially housed rats exposed to the elevated plus-maze. The anxiogenic response tomCPP (decrease in open arm entry and time and an increase in stretch attend postures) on the elevated plus-maze was greater in isolation than in socially reared controls without any concomitant difference in the hypolocomotor effect ofmCPP in the two groups.mCPP produced a greater elevation in plasma corticosterone in isolates than in group-housed controls. Hippocampal 5-HT2C receptor protein-like immunoreactive levels were significantly lower followingmCPP than saline only in rats reared in isolation. These results indicate that increased 5-HT2C receptor responsiveness accompanies isolation-rearing and may contribute to the enhanced response to stress and the increased neophobia seen in this animal model of trait anxiety/depression. In isolation reared rats, rapid down-regulation of supersensitive 5-HT2C receptors may occur in the hippocampus following 5-HT agonist challenge.
    Type of Medium: Electronic Resource
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