preproenkephalin and Depressive-Disorder

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.

Topics: Animals; Antidepressive Agents; Depressive Disorder; Disease Models, Animal; Dose-Response Relationship, Drug; Enkephalins; Male; Mice, Inbred C57BL; Morphine; Motor Activity; Naltrexone; Narcotic Antagonists; Narcotics; Nucleus Accumbens; Protein Precursors; Receptors, Opioid, kappa; RNA, Messenger; Substance Withdrawal Syndrome