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  • 2000-2004  (4)
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Year
  • 1
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd.
    Journal of neurochemistry 75 (2000), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effects of nicotine on 5-hydroxytryptamine (5-HT)release from serotonergic nerve endings in rat dorsal hippocampal slices werestudied. Nicotine (50-500 μM) caused a concentration-dependentincrease in 5-HT release. This effect was antagonised by mecamylamine (0.5μM), indicating an action at nicotinic receptors. Nicotine-evoked5-HT release was not affected by tetrodotoxin (3 μM), cadmiumchloride (0.1 mM), or the absence of Ca2+ orNa+ in the superfusion medium. Unexpectedly, higher concentrationsof mecamylamine alone (1-50 μM) increased 5-HT release. Thissuggested the presence of inhibitory input to 5-HT neurones and that theseinhibitory neurones possess tonically active nicotinic receptors. The effectof mecamylamine (50 μM) on 5-HT release was reduced by themuscarinic M1 receptor agonist, McN-A-343 (100 μM), butpirenzepine (0.005-1 μM), which blocks M1 receptors,alone increased 5-HT release. Hippocampal serotonergic neurones are known topossess both excitatory nicotinic receptors and inhibitory M1receptors. Although there may be several explanations for our results, onepossible explanation is that nicotine stimulates 5-HT release by activatingnicotinic heteroreceptors on 5-HT terminals. Mecamylamine (0.5 μM)antagonises this effect, but higher concentrations increase 5-HT releaseindirectly by blocking the action of endogenous acetylcholine on nicotinicreceptors situated on cholinergic neurones that provide muscarinic inhibitoryinput to 5-HT neurones.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 17 (2003), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This study investigated the effects of self-administered cocaine on brain reward function, measured by intracranial self-stimulation (ICSS) reward thresholds in rats. Self-administration of 10 and 20 cocaine injections (0.25 mg per injection, equivalent to 4.94 ± 0.23 and 9.88 ± 0.46 mg/kg, self-administered over 40 ± 6.9 and 99 ± 11.9 min, respectively) lowered reward thresholds 15 min later, indicating a facilitation of rewarding ICSS, but had no effect at 2, 24 or 48 h after administration. Thus, self-administration of low cocaine doses did not cause persistent changes in brain reward function. Forty cocaine injections (19.64 ± 0.94 mg/kg; self-administered over 185 ± 10.9 min) also transiently lowered reward thresholds 15 min later, while significant threshold current elevations were observed at 2 and 24 h after administration, indicating persistent withdrawal-like reward deficits. Finally, 80 cocaine injections (39.53 ± 1.84 mg/kg, self-administered over 376 ± 19.9 min) significantly elevated thresholds 2 and 48 h after self-administration, but not at 24 h. Threshold currents also tended to be elevated 15 min after self-administration. Overall, these data suggest that as the amount of self-administered cocaine increases the motivation to consume further cocaine may be shifted, from obtaining the rewarding actions of cocaine to avoidance and alleviation of a cocaine-induced negative affective state.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 12 (2000), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The purpose of the present study was to determine the role of the 5-HT1A receptors in the lateral septum in the mediation of the anxiogenic effects of nicotine in the social interaction and elevated plus maze tests of anxiety in the rat. Bilateral infusion of (–)-nicotine (4 and 8 μg) and of the 5-HT1A receptor agonist 8-OH-DPAT (200 and 500 ng) into the lateral septum decreased the time spent in social interaction, indicating anxiogenic effects. The anxiogenic effect of 8-OH-DPAT (500 ng) was completely reversed by coadministration of a behaviourally inactive dose of the 5-HT1A receptor antagonist, WAY 100635 (200 ng). The anxiogenic effect of the lower dose of (–)-nicotine (4 μg) was completely reversed by WAY 100635 (200 ng), but the reversal was only partial following administration of 8 μg nicotine. In a second test of anxiety, the elevated plus maze, lateral septal administration of 8-OH-DPAT (500 ng) and nicotine (4 μg) induced anxiogenic effects. In this test, the anxiogenic effect of nicotine (4 μg) was completely reversed by coadministration of WAY 100635 (200 ng). The effects of 8-OH-DPAT demonstrate that stimulation of 5-HT1A receptors in the lateral septum has anxiogenic effects in two animal tests and that the anxiogenic effects of nicotine are mediated at least in part by these 5-HT1A receptors.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 13 (2001), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The 5-HT1A receptor has previously been shown to be important in mediating the behavioural effects of nicotine. It is possible that nicotine administration might regulate the levels of 5-HT receptors in limbic and cortical regions, and such regulations may underlie adaptive responses to nicotine in the central nervous system. The effects of acute and chronic systemic (–)-nicotine administration on 5-HT1A receptor gene expression were measured by in situ hybridization, in the rat cerebral cortex, dorsal hippocampus and lateral septum. In the cortex, acute nicotine (0.5 mg/kg i.p.) significantly increased the expression of 5-HT1A receptor mRNA 2 h and 24 h after injection. Similarly, acute nicotine significantly increased 5-HT1A receptor mRNA in the dentate gyrus (DG), CA3 and CA1 regions of the dorsal hippocampus 2 h and 24 h after injection. Acute nicotine was without effect in the lateral septum. Chronic nicotine (0.5 mg/kg i.p; twice daily for 7 days) significantly decreased 5-HT1A receptor mRNA in the cortex 2 h after the final injection, but was without effect at 24 h or 72 h. Chronic nicotine caused no changes in 5-HT1A mRNA in the lateral septum or dorsal hippocampus. These data demonstrate that nicotine regulates 5-HT1A receptor gene expression in the cortex and hippocampus. The rapid regulation of expression of 5-HT1A receptor mRNA leads to the hypothesis that nicotine-induced 5-HT release may alter the postsynaptic sensitivity to 5-HT.
    Type of Medium: Electronic Resource
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