Involvement of dopamine D2 receptor signal transduction in the discriminative stimulus effects of the κ-opioid receptor agonist U-50,488H in rats.
Behav Pharmacol
; 24(4): 275-81, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23838963
ABSTRACT
We have reported previously that the inhibition of both dopaminergic and psychotomimetic/hallucinogenic components plays a role in the discriminative stimulus effects of U-50,488H. However, the mechanisms that underlie the discriminative stimulus effects of U-50,488H, and especially the component that plays a significant role, have not yet been clarified. The present study was designed to further investigate the mechanism(s) of the discriminative stimulus effects of the κ-opioid receptor agonist U-50,488H in rats that had been trained to discriminate between 3.0 mg/kg U-50,488H and saline. The dopamine D2 receptor antagonist sulpiride, but not the D1 receptor antagonist SCH23390, generalized to the discriminative stimulus effects of U-50,488H. The mood-stabilizing agents lithium chloride and valproic acid, which have attenuating effects on the Akt/GSK3 pathway, also partially generalized to the discriminative stimulus effects of U-50,488H. In contrast, the 5-HT-related compound racemic 3,4-methylenedioxymethamphetamine, the cannabinoid receptor agonist WIN55,212-2, and the µ-opioid receptor agonist morphine failed to generalize to the discriminative stimulus effects of U-50,488H. These results suggest that the inhibition of the dopaminergic activity mediated by the postsynaptic D2 receptor, followed by suppression of the Akt/GSK3 pathway may be critical for the induction of the discriminative stimulus effects induced by U-50,488H.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Receptores de Dopamina D2
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Analgésicos não Narcóticos
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(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida
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Discriminação Psicológica
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article