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Antagonism of κ Opioid Receptor in the Nucleus Accumbens Prevents the Depressive-Like Behaviors Following Prolonged Morphine Abstinence

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Antagonism of κ Opioid Receptor in the Nucleus Accumbens Prevents the Depressive-Like Behaviors Following Prolonged Morphine Abstinence

Gui-Ying Zan et al. Behav Brain Res.

Abstract

The association between morphine withdrawal and depressive-like symptoms is well documented, however, the role of dynorphin/κ opioid receptor system and the underlying neural substrates have not been fully understood. In the present study, we found that four weeks morphine abstinence after a chronic escalating morphine regimen significantly induced depressive-like behaviors in mice. Prodynorphin mRNA and protein levels were increased in the nucleus accumbens (NAc) after four weeks of morphine withdrawal. Local injection of κ opioid receptor antagonist nor-Binaltorphimine (norBNI) in the NAc significantly blocked the expression of depressive-like behaviors without influencing general locomotor activity. Thus, the present study extends previous findings by showing that prolonged morphine withdrawal-induced depressive-like behaviors are regulated by dynorphin/κ opioid receptor system, and shed light on the κ opioid receptor antagonists as potential therapeutic agents for the treatment of depressive-like behaviors induced by opiate withdrawal.

Keywords: Depression; Morphine withdrawal; Nucleus accumbens; Prodynorphin; κ Opioid receptor.

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