The compulsion zone explains the self-administration of cocaine, RTI-55 and bupropion in rats.
Brain Res
; 1774: 147707, 2022 01 01.
Article
em En
| MEDLINE
| ID: mdl-34736890
ABSTRACT
Rats that reliably self-administered cocaine also reliably self-administered the cocaine analog RTI-55 and bupropion. The inter-injection intervals of these dopamine transporter (DAT) inhibitors were regular at a given unit dose and increased as a function of unit dose. However, the mean rate of intake differed widely, ranging from 731 to 459 to 2.1 nmol/kgâmin-1 for bupropion, cocaine and RTI-55 respectively, a dramatic 348-fold range. An analysis of inter-injection intervals as a function of unit dose generated values for the mean satiety threshold of 50.6, 5.1 and 0.7 nmol/kg and t1/2 of 56.7, 9.3 and 255.6 min for bupropion, cocaine and RTI-55, respectively. The difference in rate of intake of bupropion and RTI-55 relative to cocaine is a product of their 0.1 and 7.3 fold difference in PD potency and their 6.1 and 27.5 fold difference in t1/2. Additionally, the relative durations of lever-pressing following termination of drug access correlated with the t1/2 estimates. It is hypothesized this duration represents the time required for the drug concentration to fall from the satiety threshold below the priming threshold (the minimum DAT inhibitor level that will induce lever-pressing). This indicates that the time needed for an animal to cease lever pressing following termination of access to the DAT inhibitor is predominately a function of the PK properties of the agonist. The self-administration behavior paradigm in the context of the compulsion zone theory can be used as a bioassay to determine the PK/PD properties of indirect dopamine receptor agonists.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Recompensa
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Comportamento Animal
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Bupropiona
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Cocaína
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Comportamento Compulsivo
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Inibidores da Captação de Dopamina
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article