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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacological interactions between serotonin and dopamine on behavior in the squirrel monkey (1997)
    Springer
    Psychopharmacology 131 (1997), S. 40-48 
    Details
    ISSN: 1432-2072
    Keywords: Key words Apomorphine ; Dopamine ; Drug self-administration ; Fixed-interval schedule ; GBR 12909 ; Operant behavior ; Quinpirole ; Second-order schedule ; Serotonin ; Squirrel monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The behavioral effects of GBR 12909, a selective dopamine uptake inhibitor, were determined in squirrel monkeys trained to respond under a fixed-interval (FI) schedule of stimulus termination and a second-order schedule of IV drug self-administration. Intermediate doses of GBR 12909 increased FI response rate markedly, and the highest dose decreased response rate below control values. The 5HT uptake inhibitors, alaproclate and fluoxetine, and the 5HT agonist, quipazine, attenuated the behavioral-stimulant effects of GBR 12909, whereas the 5HT2A/2C antagonist, ritanserin, enhanced the behavioral-stimulant effects of the lowest dose. GBR 12909 reliably maintained self-administration, and ritanserin increased response rate maintained by the highest dose. The dopamine agonist, quinpirole, increased FI response rate in only one of three subjects, and ritanserin enhanced the behavioral-stimulant effects of quinpirole in that subject. The dopamine agonist, apomorphine, only decreased FI response rate, and ritanserin did not alter its behavioral effects. The pharmacological profile of GBR 12909 administered alone and in combination with selective 5HT drugs in the present study was similar to that obtained previously with cocaine, further demonstrating that 5HT can reliably modulate the behavioral effects of psychomotor stimulants with prominent dopaminergic actions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050263
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  • 2
    Electronic Resource
    Electronic Resource
    Cocaine-induced changes in extracellular dopamine determined by microdialysis in awake squirrel monkeys (2000)
    Springer
    Psychopharmacology 148 (2000), S. 299-306 
    Details
    ISSN: 1432-2072
    Keywords: Key words Microdialysis ; Squirrel monkey ; Cocaine ; GBR 12909 ; Dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: The behavioral effects of cocaine have been linked to brain dopamine systems. Extending the findings to neurochemical studies in the squirrel monkey would enhance our understanding of the behavioral pharmacology of cocaine in nonhuman primates. Objectives: The present studies characterized the effects of cocaine and the selective dopamine uptake inhibitor GBR 12909 on extracellular dopamine in the caudate nucleus of awake squirrel monkeys through microdialysis experiments. Methods: Guide cannulae were implanted in the caudate nucleus of four monkeys using a stereotaxic apparatus and coordinates obtained from a standard squirrel monkey brain atlas. Accurate probe placement was confirmed in all subjects with magnetic resonance imaging. Results: Collectively, the results support the feasibility of a repeated-measures design. Stability of tissue integrity after repeated probe insertion was supported by measurement of consistent basal levels of dopamine and its metabolites across several experiments, observation of potassium-induced dopamine release and absence of significant glial proliferation as assessed by GFAP (glial fibrillary acidic protein) immunochemistry. Moreover, peak drug effects and time-course of action were similar when multiple probes were positioned in the same anatomical site over several experiments. Cocaine (1.0 mg/kg i.m.) and GBR 12909 (3.0 mg/kg i.m.) elevated extracellular dopamine to approximately 300% of basal levels, but GBR 12909 produced a slower, more sustained elevation than cocaine. Conclusions: The results validate the use of microdialysis in awake primates using repeated sampling of the same anatomical site and demonstrate orderly changes in extracellular dopamine following administration of dopamine uptake inhibitors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050054
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  • 3
    Electronic Resource
    Electronic Resource
    Behavioral and physiological effects of xanthines in nonhuman primates (1997)
    Springer
    Psychopharmacology 129 (1997), S. 1-14 
    Details
    ISSN: 1432-2072
    Keywords: Key words Caffeine ; Xanthines ; Adenosine antagonist ; Phosphodiesterase inhibition ; Operant behavior ; Respiration ; Cardiovascular system ; Nonhuman primates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Caffeine and related xanthines can have significant behavioral effects on measures of locomotor activity, schedule-controlled behavior, drug self-administration, and learning and memory. Xanthines also produce numerous physiological effects including positive inotropic and chronotropic effects on the heart, decreased airway resistance in the lung, and respiratory stimulation. Due to the widespread use of xanthines as constituents of food and beverages and as therapeutic drugs, identification of mechanisms that mediate their pharmacological effects has considerable relevance for drug development and therapeutics. Two primary mechanisms involving the cyclic nucleotide system have been implicated as the bases for the effects of xanthines in the CNS. Many xanthines bind to specific adenosine recognition sites and block the actions of adenosine. Xanthines also inhibit cyclic nucleotide phosphodiesterases, the enzymes responsible for the hydrolytic inactivation of cyclic AMP and cyclic GMP. Recent research in nonhuman primates has characterized the behavioral, respiratory and cardiovascular effects of a number of xanthines and related drugs differing in affinity at different subtypes of adenosine receptors and in capacity to inhibit different molecular forms of PDE. The behavioral-stimulant effects of xanthines appear to be mediated principally by their adenosine-antagonist actions and may be limited by PDE inhibition. The respiratory-stimulant and cardiac effects of xanthines, on the other hand, appear to be linked more closely to their PDE- inhibiting actions than to adenosine antagonism. Converging lines of evidence suggest that adenosine A2 and cAMP-specific (possibly type IV) PDE mechanisms play especially prominent roles in mediating the behavioral and physiological effects of xanthines in nonhuman primates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050155
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Serotonergic modulation of the discriminative-stimulus effects of cocaine in squirrel monkeys (1997)
    Springer
    Psychopharmacology 132 (1997), S. 27-34 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Serotonin ; Drug discrimination ; Squirrel monkey ; Quipazine ; Fluoxetine ; Ketanserin ; Ritanserin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In order to investigate the potential modulatory role of serotonin on the discriminative-stimulus effects of cocaine, two groups of squirrel monkeys were trained to discriminate 0.3 mg/kg or 1.0 mg/kg cocaine and saline under a two-lever drug-discrimination procedure. Substitution of a range of cocaine doses (0.03–1.7 mg/kg) occasioned orderly, dose-dependent increases in cocaine-lever responding. When administered alone, the non-selective serotonin direct agonist, quipa- zine, also occasioned increases in cocaine-lever responding which were more pronounced in subjects trained with the lower cocaine dose. When quipazine was administered in combination with cocaine, there was an increase in cocaine-lever responding, indicating an additive effect. The serotonin uptake inhibitor, fluoxetine, occasioned saline-lever responding when administered alone. However, in combination with cocaine, fluoxetine enhanced the discriminative effects of cocaine in subjects trained at the lower cocaine dose. The 5-HT2-selective antagonists, ketanserin and ritanserin, did not occasion cocaine-lever responding when administered alone. In combination with cocaine, ketanserin attenuated the discriminative effects of cocaine in most subjects, and ritanserin attenuated the discriminative effects of cocaine in subjects trained at the higher dose. These results indicate that the discriminative-stimulus effects of cocaine may be increased by direct- and indirect-acting serotonin agonists and attenuated by serotonin antagonists in squirrel monkeys.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050316
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    Paper (German National Licenses)
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