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  • 1
    Digitale Medien
    Digitale Medien
    Oxford UK : Blackwell Science Ltd.
    Journal of neurochemistry 75 (2000), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 17 (2003), S. 0 
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 12 (2000), S. 0 
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 13 (2001), S. 0 
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 11 (1999), S. 0 
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: The present study investigated the role of nicotinic receptors in the lateral septum in the modulation of anxiety. The effects of direct injections of nicotine into the lateral septum were first investigated in two tests of anxiety, social interaction and elevated plus-maze tests. Intra-septal injection of nicotine (1 and 4 μg) induced consistent anxiogenic effects in both tests. The reversal of nicotinic effects with mecamylamine was then studied in the social interaction test. Intra-septal injection of mecamylamine at a low dose (15 ng) induced an anxiolytic effect, suggesting the presence of intrinsic cholinergic tone increasing anxiety. At higher doses (30–50 ng), mecamylamine was without effect in the social interaction test, but blocked the anxiogenic effects of nicotine (4 μg). These findings provide further evidence for the role of the lateral septum in the modulation of anxiety and suggest that cholinergic projections to this brain area facilitate anxiety through nicotinic receptors.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-2072
    Schlagwort(e): Key words Nicotinic receptor ; Dorsal hippocampus ; Anxiety ; Phobia ; Elevated plus-maze ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract   Rationale: The elevated plus-maze provides a test situation in which distinctive states of anxiety are elicited on trials 1 and 2 and the dorsal hippocampus has previously been shown to mediate the anxiogenic effects of (–)-nicotine in the social interaction test. Objective: To determine the effects of a wide dose range of (–)-nicotine on trial 1 and 2 in the plus-maze after systemic administration and whether the dorsal hippocampus is a site mediating the anxiogenic effect of nicotine. Methods: (–)-Nicotine (0.001, 0.005, 0.01, 0.05, 0.1, 0.5 and 1 mg/kg) was injected IP 30 min before testing for 5 min in the plus-maze. Rats receiving dorsal hippocampal infusions received bilateral infusions of 0.5 μl of artificial CSF or (–)-nicotine (0.1, 1, 4 or 8 μg). The needle was left in place for 50 s after injection and testing took place 3 min later. Rats tested on trial 1 were naive to the plus-maze, those tested on trial 2 had received a previous 5-min undrugged exposure to the maze 48 h earlier. Results: Low doses of (–)-nicotine (0.001, 0.005, 0.01, 0.05 and 0.1 mg/kg, IP) were without effect on either trial, but higher doses (0.5 and 1 mg/kg, IP) had anxiogenic effects on both trials, as shown by decreases in percentage time spent and percentage entries onto the open arms. Infusion of (–)-nicotine (0.1, 1, 4 and 8 μg) bilaterally into the dorsal hippocampus was without effect on trial 1, but 1 μg had an anxiolytic effect on trial 2, shown by an increased percentage time spent on the open arms. Conclusions: The results on both trials in the plus-maze after systemic administration of nicotine add to previous reports from the social interaction test that high doses of nicotine have anxiogenic effects. However, the effects of nicotine in the dorsal hippocampus are different in all three anxiety tests (anxiogenic in social interaction, ineffective on trial 1, anxiolytic on trial 2) showing that nicotinic cholinergic control in this brain region may vary depending on the state and/or type of anxiety generated by the test. The brain region(s) underlying the anxiogenic effects of IP nicotine on both trials in the plus-maze remain to be identified.
    Materialart: Digitale Medien
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