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, 39 (9), 645-53

Brain Reward Circuits in Morphine Addiction


Brain Reward Circuits in Morphine Addiction

Juhwan Kim et al. Mol Cells.


Morphine is the most potent analgesic for chronic pain, but its clinical use has been limited by the opiate's innate tendency to produce tolerance, severe withdrawal symptoms and rewarding properties with a high risk of relapse. To understand the addictive properties of morphine, past studies have focused on relevant molecular and cellular changes in the brain, highlighting the functional roles of reward-related brain regions. Given the accumulated findings, a recent, emerging trend in morphine research is that of examining the dynamics of neuronal interactions in brain reward circuits under the influence of morphine action. In this review, we highlight recent findings on the roles of several reward circuits involved in morphine addiction based on pharmacological, molecular and physiological evidences.

Keywords: addiction; morphine; opiate; reward circuits; withdrawal symptom.


Fig. 1.
Fig. 1.
Schematic diagram of brain reward circuits involved in morphine reward. The ventral tegmental area (VTA) projects dopaminergic (purple) transmission to the nucleus accumbens (NAc), medial prefrontal cortex (mPFC), hippocampus (Hipp), bed nucleus of the stria terminalis (BNST), amygdala (Amy), dorsal striatum (dST) and it modulates glutamatergic (blue) and gamma-aminobutyric acid (GABA) ergic (green) transmission. VTA dopaminergic (DA) neurons are also modulated by lateral hypothalamus (LH) orexinergic (yellow) neurons and rostromedial tegmental nucleus (RMTg) GABAergic neurons. Glutamatergic projections from the mPFC and Amy innervate the NAc to modulate NAc GABAergic transmission to the VTA, and glutamatergic transmission from the mPFC and BNST modulates VTA DA neurons.

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    1. Ahmad T., Lauzon N.M., de Jaeger X., Laviolette S.R. Cannabinoid transmission in the prelimbic cortex bidirectionally controls opiate reward and aversion signaling through dissociable kappa versus mu-opiate receptor dependent mechanisms. J. Neurosci. 2013;33:15642–15651. - PMC - PubMed
    1. Ambroggi F., Ishikawa A., Fields H.L., Nicola S.M. Basolateral amygdala neurons facilitate reward-seeking behavior by exciting nucleus accumbens neurons. Neuron. 2008;59:648–661. - PMC - PubMed
    1. Amunts K., Kedo O., Kindler M., Pieperhoff P., Mohlberg H., Shah N.J., Habel U., Schneider F., Zilles K. Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps. Anat. Embryol. (Berl.) 2005;210:343–352. - PubMed
    1. Baimel C., Borgland S.L. Orexin signaling in the VTA gates morphine-induced synaptic plasticity. J. Neurosci. 2015;35:7295–7303. - PMC - PubMed
    1. Beitner-Johnson D., Nestler E.J. Morphine and cocaine exert common chronic actions on tyrosine hydroxylase in dopaminergic brain reward regions. J. Neurochem. 1991;57:344–347. - PubMed

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