doi:

DOI: 10.3724/SP.J.1042.2019.00060

Advances in Psychological Science (心理科学进展) 2019/27:1 PP.60-69

Reward circuits and opioid addiction: The moderating effect of the rostromedial tegmental nucleus


Abstract:
The rostromedial tegmental nucleus (RMTg) is located caudally to the ventral tegmental area (VTA), which is rich in inhibitory γ-aminobutyric acid (GABAergic) neurons. The RMTg is an integrative modulator of the mesolimbic dopamine system. Its GABAergic neurons receive input from the lateral habenula (LHb) and then project to VTA dopaminergic neurons, which inhibits the release of dopamine. These three brain areas are an important part of the reward circuit, in which the RMTg plays a particularly important role in reward circuits activated by opioids. GABA neurons in the RMTg are strongly inhibited by opioids, and this is followed by disinhibition of VTA dopaminergic neurons, which activates the reward system. Therefore, the RMTg is a potentially important target for the treatment of drug addiction (especially opioid addiction). Furthermore, cholinergic feedback to the RMTg, acting on muscarinic receptors, can be inhibitory for an opioid-induced reward effect. Future studies should further explore the negative reward circuit regulated by the RMTg, which is of great significance for weakening drug-seeking motivation and promoting extinction and withdrawal.

Key words:reward circuits,rostromedial tegmental nucleus,GABAergic neurons,lateral habenula,opioid addiction

ReleaseDate:2019-01-28 10:22:47



Adamantidis, A. R., Tsai, H-C., Boutrel, B., Zhang, F., Stuber, G. D., Budygin, E. A., … de Lecea, L. (2011). Optogenetic interrogation of dopaminergic modulation of the multiple phases of reward-seeking behavior. The Journal of Neuroscience, 31(30), 10829-10835.

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA:American Psychiatric Publishing.

Balcita-Pedicino, J. J., Omelchenko, N., Bell, R., & Sesack, S. R. (2015). The inhibitory influence of the lateral habenula on midbrain dopamine cells:Ultrastructural evidence for indirect mediation via the rostromedial mesopontine tegmental nucleus. Journal of Comparative Neurology, 519(6), 1143-1164.

Bourdy, R., & Barrot, M. (2012). A new control center for dopaminergic systems:Pulling the VTA by the tail. Trends in Neurosciences, 35(11), 681-690.

Bowers, M. S., Chen, B. T., & Bonci, A. (2010). AMPA receptor synaptic plasticity induced by psychostimulants:The past, present, and therapeutic future. Neuron, 67(1), 11-24.

Brown, P. L., Palacorolla, H., Brady, D., Riegger, K., Elmer, G. I., & Shepard, P. D. (2017). Habenula-induced inhibition of midbrain dopamine neurons is diminished by lesions of the rostromedial tegmental nucleus. The Journal of Neuroscience, 37(1), 217-225.

Fields, H. L., & Margolis, E. B. (2015). Understanding opioid reward. Trends in Neurosciences, 38(4), 217-225.

Friedman, A., Lax, E., Dikshtein, Y., Abraham, L., Flaumenhaft, Y., Sudai, E., … Yadid, G. (2010). Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior. Neuropharmacology, 59(6), 452-459.

Gysling, K., & Wang, R. Y. (1983). Morphine-induced activation of A10 dopamine neurons in the rat. Brain Research, 277(1), 119-127.

Haber, S. N., & Knutson, B. (2009). The reward circuit:Linking primate anatomy and human imaging. Neuropsychopharmacology, 35, 4-26.

Hong, S., & Hikosaka, O. (2008). The globus pallidus sends reward-related signals to the lateral habenula. Neuron, 60(4), 720-729.

Hong, S., Jhou, T. C., Smith, M., Saleem, K. S., & Hikosaka, O. (2011). Negative reward signals from lateral habenula to dopamine neurons are mediated by rostromedial tegmental nucleus in primates. The Journal of Neuroscience, 31(32), 11457-11471.

Huff, M. L., & LaLumiere, R. T. (2015). The rostromedial tegmental nucleus modulates behavioral inhibition following cocaine self-administration in rats. Neuropsychopharmacology, 40(4), 861-873.

Ikemoto, S., & Bonci, A. (2014). Neurocircuitry of drug reward. Neuropharmacology, 76(Part B), 329-341.

Jalabert, M., Bourdy, R., Courtin, J., Veinante, P., Manzoni, O. J., Barrot, M., & Georges, F. (2011). Neuronal circuits underlying acute morphine action on dopamine neurons. Proceedings of the National Academy of Sciences of the United States of America, 108(39), 16446-16450.

Jennings, J. H., Sparta, D. R., Stamatakis, A. M., Ung, R. L., Pleil, K. E., Kash, T. L., & Stuber, G. D. (2013). Distinct extended amygdala circuits for divergent motivational states. Nature, 496(7444), 224-228.

Jhou, T. C., Fields, H. L., Baxter, M. G., Saper, C. B., & Holland, P. C. (2009). The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine neurons, encodes aversive stimuli and inhibits motor responses. Neuron, 61(5), 786-800.

Jhou, T. C., Geisler, S., Marinelli, M., Degarmo, B. A., & Zahm, D. S. (2009). The mesopontine rostromedial tegmental nucleus:A structure targeted by the lateral habenula that projects to the ventral tegmental area of Tsai and substantia nigra compacta. Journal of Comparative Neurology, 513(6), 566-596.

Jhou, T. C., Good, C. H., Rowley, C. S., Xu, S-P., Wang, H., Burnham, N. W., … Ikemoto, S. (2013). Cocaine drives aversive conditioning via delayed activation of dopamine-responsive habenular and midbrain pathways. The Journal of Neuroscience, 33(17), 7501-7512.

Ji, H., & Shepard, P. D. (2007). Lateral habenula stimulation inhibits rat midbrain dopamine neurons through a GABA (A) receptor-mediated mechanism. The Journal of Neuroscience, 27(26), 6923-6930.

Johnson, L. R., Aylward, R. L. M., Hussain, Z., & Totterdell, S. (1994). Input from the amygdala to the rat nucleus accumbens:Its relationship with tyrosine hydroxylase immunoreactivity and identified neurons. Neuroscience, 61(4), 851-865.

Johnson, S. W., & North, R. A. (1992). Opioids excite dopamine neurons by hyperpolarization of local interneurons. The Journal of Neuroscience, 12(2), 483-488.

Juarez, B., & Han, M-H. (2016). Diversity of dopaminergic neural circuits in response to drug exposure. Neuropsychopharmacology, 41(10), 2424-2446.

Kaufling, J., & Aston-Jones, G. (2015). Persistent adaptations in afferents to ventral tegmental dopamine neurons after opiate withdrawal. The Journal of Neuroscience, 35(28), 10290-10303.

Kaufling, J., Veinante, P., Pawlowski, S. A., Freund-Mercier, M-J., & Barrot, M. (2009). Afferents to the GABAergic tail of the ventral tegmental area in the rat. The Journal of Comparative Neurology, 513(6), 597-621.

Kotecki, L., Hearing, M., McCall, N. M., de Velasco, E. M. F., Pravetoni, M., Arora, D., … Wickman, K. (2015). GIRK channels modulate opioid-induced motor activity in a cell type-and subunit-dependent manner. The Journal of Neuroscience, 35(18), 7131-7142.

Lammel, S., Hetzel, A., Häckel, O., Jones, I., Liss, B., & Roeper, J. (2008). Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system. Neuron, 57(5), 760-773.

Lammel, S., Ion, D. I., Roeper, J., & Malenka, R. C. (2011). Projection-Specific modulation of dopamine neuron synapses by aversive and rewarding stimuli. Neuron, 70(5), 855-862.

Lammel, S., Lim, B. K., Ran, C., Huang, K. W., Betley, M. J., Tye, K. M., … Malenka, R. C. (2012). Input-specific control of reward and aversion in the ventral tegmental area. Nature, 491(7423), 212-217.

Lavezzi, H. N., & Zahm, D. S. (2011). The mesopontine rostromedial tegmental nucleus:An integrative modulator of the reward system. Basal Ganglia, 1(4), 191-200.

Lecca, S., Melis, M., Luchicchi, A., Ennas, M. G., Castelli, M. P., Muntoni, A. L., & Pistis, M. (2011). Effects of drugs of abuse on putative rostromedial tegmental neurons, inhibitory afferents to midbrain dopamine cells. Neuropsychopharmacology, 36(3), 589-602.

Lecca, S., Melis, M., Luchicchi, A., Muntoni, A. L., & Pistis, M. (2012). Inhibitory inputs from rostromedial tegmental neurons regulate spontaneous activity of midbrain dopamine cells and their responses to drugs of abuse. Neuropsychopharmacology, 37(5), 1164-1176.

Lobb, C. J., Wilson, C. J., & Paladini, C. A. (2010). A dynamic role for GABA receptors on the firing pattern of midbrain dopaminergic neurons. J Neurophysiol, 104(1), 403-413.

Matsui, A., Jarvie, B. C., Robinson, B. G., Hentges, S. T., & Williams, J. T. (2014). Separate GABA afferents to dopamine neurons mediate acute action of opioids, development of tolerance, and expression of withdrawal. Neuron, 82(6), 1346-1356.

Matsui, A., & Williams, J. T. (2011). Opioid-Sensitive GABA inputs from rostromedial tegmental nucleus synapse onto midbrain dopamine neurons. The Journal of Neuroscience, 31(48), 17729-17735.

Matsumoto, M., & Hikosaka, O. (2007). Lateral habenula as a source of negative reward signals in dopamine neurons. Nature, 447(7148), 1111-1115.

Matsumoto, M., & Hikosaka, O. (2009). Two types of dopamine neuron distinctly convey positive and negative motivational signals. Nature, 459(7248), 837-841.

Miesenböck, G. (2009). The optogenetic catechism. Science, 326(5951), 395-399.

Paladini, C. A., Celada, P., & Tepper, J. M. (1999). Striatal, pallidal, and pars reticulata evoked inhibition of nigrostriatal dopaminergic neurons is mediated by GABAA receptors in vivo. Neuroscience, 89(3), 799-812.

Petzel, A., Bernard, R., Poller, W. C., & Veh, R. W. (2017). Anterior and posterior parts of the rat ventral tegmental area and the rostromedial tegmental nucleus receive topographically distinct afferents from the lateral habenular complex. The Journal of Comparative neurology, 525(10), 2310-2327.

Pignatelli, M., & Bonci, A. (2015). Role of dopamine neurons in reward and aversion:A synaptic plasticity perspective. Neuron, 86(5), 1145-1157.

Rezayof, A., Nazari-Serenjeh, F., Zarrindast, M-R., Sepehri, H., & Delphi, L. (2007). Morphine-induced place preference:Involvement of cholinergic receptors of the ventral tegmental area. European Journal of Pharmacology, 562(1-2), 92-102.

Russo, S. J., & Nestler, E. J. (2013). The brain reward circuitry in mood disorders. Nature Reviews Neuroscience, 14(9), 609-625.

Sánchez-Catalán, M. J., Faivre, F., Yalcin, I., Muller, M. A., Massotte, D., Majchrzak, M., & Barrot, M. (2017). Response of the tail of the ventral tegmental area to aversive stimuli. Neuropsychopharmacology, 42(3), 638-648.

Salas, R., Baldwin, P., de Biasi, M., & Montague, P. R. (2010). BOLD responses to negative reward prediction errors in human habenula. Frontiers in Human Neuroscience, 4, 36. doi:10.3389/fnhum.2010.00036

Sanchez-Catalan, M. J., Kaufling, J., Georges, F., Veinante, P., & Barrot, M. (2014). The antero-posterior heterogeneity of the ventral tegmental area. Neuroscience, 282, 198-216.

Stamatakis, A. M., Jennings, J. H., Ung, R. L., Blair, G. A., Weinberg, R. J., Neve, R. L., … Stuber, G. D. (2013). A unique population of ventral tegmental area neurons inhibits the lateral habenula to promote reward. Neuron, 80(4), 1039-1053.

Stamatakis, A. M., & Stuber, G. D. (2012). Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance. Nature Neuroscience, 15(8), 1105-1107.

Steffensen, S. C., Svingos, A. L., Pickel, V. M., & Henriksen, S. J. (1998). Electrophysiological characterization of GABAergic neurons in the ventral tegmental area. The Journal of Neuroscience, 18(19), 8003-8015.

Steidl, S., Dhillon, E. S., Sharma, N., & Ludwig, J. (2017). Muscarinic cholinergic receptor antagonists in the VTA and RMTg have opposite effects on morphine-induced locomotion in mice. Behavioural Brain Research, 323, 111-116.

Steidl, S., Miller, A. D., Blaha, C. D., & Yeomans, J. S. (2011). M5 muscarinic receptors mediate striatal dopamine activation by ventral tegmental morphine and pedunculopontine stimulation in mice. PLoS ONE, 6(11), e27538.

Steidl, S., Myal, S., & Wise, R. A. (2015). Supplemental morphine infusion into the posterior ventral tegmentum extends the satiating effects of self-administered intravenous heroin. Pharmacology Biochemistry and Behavior, 134, 1-5.

Steidl, S., Wasserman, D. I., Blaha, C. D., & Yeomans, J. S. (2017). Opioid-induced rewards, locomotion, and dopamine activation:A proposed model for control by mesopontine and rostromedial tegmental neurons. Neuroscience & Biobehavioral Reviews, 83, 72-82.

Steinberg, E. E., Keiflin, R., Boivin, J. R., Witten, I. B., Deisseroth, K., & Janak, P. H. (2013). A causal link between prediction errors, dopamine neurons and learning. Nature Neuroscience, 16(7), 966-973.

Wasserman, D. I., Tan, J. M. J., Kim, J. C., & Yeomans, J. S. (2016). Muscarinic control of rostromedial tegmental nucleus GABA neurons and morphine-induced locomotion. European Journal of Neuroscience, 44(1), 1761-1770.

Wasserman, D. I., Wang, H. G., Rashid, A. J., Josselyn, S. A., & Yeomans, J. S. (2013). Cholinergic control of morphine-induced locomotion in rostromedial tegmental nucleus versus ventral tegmental area sites. European Journal of Neuroscience, 38(5), 2774-2785.

World Health Organ. (2010). ATLAS on substance use (2010):Resources for the prevention and treatment of substance use disorders. World Health Organ, Geneva.