부산대학교 도서관

Opiate addiction develops as a chronic relapsing disorder upon drug recreational use or following misuse of analgesic prescription. Mu opioid (MOP) receptors are the primary molecular target of opiates but increasing evidence support in vivo functional heteromerization with the delta opioid (DOP) receptor, which may be part of the neurobiological processes underlying opiate addiction. Here, we used double knock-in mice co-expressing fluorescent versions of the MOP and DOP receptors to examine the impact of chronic morphine administration on the distribution of neurons co-expressing the two receptors. Our data show that MOP/DOP neuronal co-expression is broader in morphine-dependent mice and is detected in novel brain areas located in circuits related to drug reward, motor activity, visceral control and emotional processing underlying withdrawal. After four weeks of abstinence, MOP/DOP neuronal co-expression is still detectable in a large number of these brain areas except in the motor circuit. Importantly, chronic morphine administration increased the proportion of MOP/DOP neurons in the brainstem of morphine-dependent and abstinent mice. These findings establish persistent changes in the abstinent state that may modulate relapse and opiate-induced hyperalgesia and also point to the therapeutic potential of MOP/DOP targeting. This article is part of the Special Issue entitled 'Receptor heteromers and their allosteric receptor-receptor interactions'. Image 1 • Mu-delta neuronal co-expression is broadened in morphine-dependent mice. • Most changes in mu-delta neuronal distribution remain in morphine abstinent mice. • Mu-delta neuronal distribution is enlarged in the forebrain. • The proportion of mu-delta neurons is increased in the hindbrain. • Mu-delta neurons are involved in somatic and emotional processing. [ABSTRACT FROM AUTHOR]