Competitive dopamine receptor antagonists increase the equiactive cocaine concentration during self-administration
| Autor: | Mantana K. Norman, Michael R. Tabet, Amadeo J. Pesce, Andrew B. Norman, Vladimir L. Tsibulsky |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Kinetics Acceleration (differential geometry) Self Administration Pharmacology Article Rats Sprague-Dawley Cellular and Molecular Neuroscience Eticlopride Cocaine Dopamine Uptake Inhibitors Internal medicine Salicylamides medicine Animals Drug Interactions Steady state level Dopamine receptor antagonist Analysis of Variance Behavior Animal Dose-Response Relationship Drug Drug Administration Routes Antagonist Age Factors Benzazepines Rats Endocrinology Dopamine receptor Conditioning Operant Dopamine Antagonists Self-administration Psychology |
| Zdroj: | Synapse (New York, N.Y.). 65(5) |
| ISSN: | 1098-2396 |
| Popis: | Competitive dopamine receptor antagonists increase the rate of cocaine self-administration. As the rate of self-administration at a particular unit dose is determined by the satiety threshold and the elimination half-life (t1/2) of cocaine, we investigated whether dopamine receptor antagonists altered these parameters. The plasma cocaine concentration at the time of each self-administration was constant during a session demonstrating that this satiety threshold concentration represents an equiactive cocaine concentration. The plasma cocaine concentration at the time of self-administration was increased by {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390, consistent with pharmacological theory. In rats trained to reliably self-administer cocaine, {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 had no effect on the plasma steady-state cocaine concentration produced by constant infusions of cocaine. Therefore, this antagonist had no effect on cocaine t1/2 at a dose that accelerated cocaine self-administration. A continuous cocaine infusion at a rate that maintained steady state concentrations above the satiety threshold stopped self-administration. {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390, or the D2 dopamine receptor antagonist (−) eticlopride, reinstated self-administration in the presence of the constant cocaine infusion. This is consistent with {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 and eticlopride raising the satiety threshold above the steady state level produced by the constant cocaine infusion. It is concluded that the antagonist-induced acceleration of cocaine self-administration is the result of a pharmacokinetic/pharmacodynamic interaction whereby the rate of cocaine elimination is faster at the higher concentrations, as dictated by first-order kinetics, so that cocaine levels decline more rapidly to the elevated satiety threshold. This results in the decreased inter-injection intervals. |
| Databáze: | OpenAIRE |
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