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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Neuroadaptive changes underlying repeated exposure to cocaine-induced behavioural sensitization have been related to modification in the pattern of synaptic connectivity and excitatory transmission. Remarkably, even a single exposure to abused drugs is sufficient to elicit lasting behavioural sensitization. The present study investigated whether in Sprague–Dawley rats a single, behavioural sensitizing dose of cocaine is sufficient to induce changes in the mRNA levels of growth-associated protein 43 (GAP-43), an important protein in mediating experience-dependent plasticity and synaptic reorganization, and of glutamate receptor 1 (GluR1), a subunit of AMPA glutamate receptors, a protein that is up-regulated with repeated cocaine. Single exposure to 20, but not 10 mg/kg cocaine induced locomotor sensitization to a second injection of 10 mg/kg cocaine, observed at 24 h, 48 h and 7 days. Single dose of 20 but not 10 mg/kg cocaine 48 h before scheduled death significantly enhanced GluR1 and GAP-43 mRNA expression in the nucleus accumbens (NAc), both shell and core subregions, and ventral tegmental area (VTA). No changes were found in the levels of mRNA for GluR1 and GAP-43 in the frontal cortex, caudate putamen, dentate gyrus of hippocampus and basolateral nucleus of the amygdala after the single dose of 20 mg/kg cocaine. These results further strengthen the involvement of NAc and VTA in the behavioural sensitization and suggest a role of GAP-43 in the synaptic reorganization associated to drug abuse.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 94 (1988), S. 359-364 
    ISSN: 1432-2072
    Keywords: Serotonin synthesis ; Dopamine synthesis ; RU-24969 ; Anxiety ; Antidepressant activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The regional brain synthesis of serotonin (5-HT) and dopamine (DA) was studied in rats after various doses of 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU-24969), a 5-HT1 receptor agonist. The potential anxiolytic and antidepressant properties of the compound were examined as well. RU-24969 0.62 mg/kg significantly reduced 5-HT synthesis in the nucleus accumbens and hypothalamus, while with 1.25 and 2.5 mg/kg the effect was also seen in striatum, hippocampus, brainstem and cortex. RU-24969 2.5 and 5 mg/kg had no effect on DA synthesis in the striatum, while 5.0 mg/kg significantly increased it in the nucleus accumbens. At doses of 2.5 and 5.0 mg/kg the drug increased the motor activity of rats measured during 1 h in activity cages while 0.625 and 1.25 mg/kg had no effect. Doses ranging from 0.62 to 2.5 mg/kg RU-24969 significantly reduced unpunished responding in a test of conditioned suppression of drinking. Doses of 1.25 and 2.5 mg/kg also reduced punished responding. Finally, of various doses only 2.5 mg/kg RU-24969 significantly reduced the duration of immobility of rats in the forced swimming test but the effects were due to running around the cylinder rather than to escape attempts. In conclusion, RU-24969 reduced 5-HT synthesis in all brain areas examined, with a preferential effect for the nucleus accumbens and the hypothalamus. At higher doses, there was also a specific increase in DA synthesis in the nucleus accumbens. The compound raised the level of activity of rats but no clear evidence of any potential anxiolytic or antidepressant properties has been obtained.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 88 (1986), S. 196-200 
    ISSN: 1432-2072
    Keywords: Amphetamine ; Discriminative stimulus ; Rats ; Neurochemistry ; Dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus properties ofd-amphetamine, cocaine, and apomorphine were assessed in rats trained in a two-lever, food-reinforced drug discrimination paradigm to discriminate 1.0 mg/kgd-amphetamine from saline. After determination of these dose-response relationships, the rats were divided into two groups. One group (6-OHDA) was given injections of desmethylimipramine (DMI, 30 mg/kg, IP) and 6-hydroxydopamine (6-OHDA, 100 μg/10 μl each ventricle), while the other group (sham) was given the same dose of DMI and 6-OHDA vehicle (intraventricularly). Beginning approximately 45 days after intraventricular injections, dose-response relationships were redetermined for all three drugs. Larger doses ofd-amphetamine were required to elicit the same response in the 6-OHDA group (i.e. the dose-response relationship was shifted to the right), while no change was observed in the sham group. Any changes in the dose-response relationships for cocaine and apomorphine were comparable in the 6-OHDA and sham group. The rate-decreasing effects were not altered in either group for any of the drugs. Upon sacrifice, dopamine (DA) was found to be significantly depleted in the accumbens, caudate and rest of brain of the 6-OHDA group. Levels of norepinephrine and serotonin were unaltered. These data suggest that central DA-containing neurons play a role in the discriminative stimulus properties of psychomotor stimulants in rats.
    Type of Medium: Electronic Resource
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