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Activatinga neural pathway from the Ventral Tegmental Area (VTA) to the Dorsal RapheNucleus (DRN) could significantly reduce morphine addiction while not affectingits analgesic effect, suggests new research led by Prof. LI Xiaoming fromZJU’s School of Medicine.

Thestudy, published in the January 10 issue of Neuron, found two parallel inhibitoryneural pathways from VTA to DRN: The rostral VTA (rVTA) sends more projections to the DRNGABAergic neurons, whereas the caudal VTA (cVTA) innervate more serotonergicneurons in the DRN. The former pathway was discovered to be specificallyinvolved in morphine addiction.

Explorationof neural pathway

VTAand DRN are two important nuclei in the brain that participate in theregulation of emotion, cognition, memory and motor functions, especially in thereward and addiction pathway. The interaction between VTA and DRN has been anarea of much scientific interest.

Assuch, the team adopted retrograde tracing on the brain. “We first used theretrograde tracing to track the whole brain projections of DRN, and found therewere two populations of GABAergic neurons in VTA projection to DRN. RVTAand cVTA GABAergic projections in the DRN exhibited opposite functions inreward-related behaviors, probably by contrasting regulation of DRNserotonergic neuronal activity,” said Dr. LI Yue, one of the first authors ofthe article.

Additionally, the teamfound that morphine receptors (MOPs) were differentially distributed in therostral and caudal VTA GABAergic neuronal terminals within DRN, resulting indifferent modulation of these two circuits by chronic morphine exposure.Chemo-genetic activation of the rVTA→DRN inhibitory circuit blockedmorphine-induced CPP (Condition Place Preferance) without affecting otherbehaviors.

“Ourresults identified the rVTA→DRN inhibitory circuit as another key systemmediating morphine reward. Activating this pathway during opioid administrationmay be a new strategy to reduce the addiction properties without affecting theanalgesic effects of morphine,” explained LI Chunyue, another team member.

Reviewers of Neuron magazinecommented on the research as being “technicallysophisticated” anda “timely study of the anatomy physiology of this system”.

VTA→DRN andmorphine addiction

Additionally,the team found that morphine receptors (MOPs) were differentially distributedin the rostral and caudal VTA GABAergic neuronal terminals within DRN,resulting in different modulation of these two circuits by chronic morphineexposure. Chemo-genetic activation of the rVTA→DRN inhibitory circuit blockedmorphine-induced CPP (Condition Place Preferance) without affecting otherbehaviors.

“Ourresults identified the rVTA→DRN inhibitory circuit as another key systemmediating morphine reward. Activating this pathway during opioid administrationmay be a new strategy to reduce the addiction properties without affecting theanalgesic effects of morphine,” explained LI Chunyue, another team member.

Reviewers of Neuron magazinecommented on the research as being “technicallysophisticated” anda “timely study of the anatomy physiology of this system”.

The study was funded bythe National Natural Science Foundation of China and is one of the key projectsof NSFC's “MajorResearch Plan for Emotionand Memory Neural Circuits Base”.

Source: School of Medicine

Editor: IanChew