Effects of GABAB receptor blockade on lateral habenula glutamatergic neuron activity following morphine injection in the rat: an electrophysiological study
Abstract
Background and purpose: The lateral habenula (LHb), a key area in the regulation of the reward system, exerts a major influence on midbrain neurons. It has been shown that the gamma-aminobutyric acid (GABA)-ergic system plays the main role in morphine dependency. The role of GABA type B receptors (GABABRs) in the regulation of LHb neural activity in response to morphine, remains unknown. In this study, the effect of GABABRs blockade in response to morphine was assessed on the neuronal activity in the LHb.
Experimental approach: The baseline firing rate was recorded for 15 min, then morphine (5 mg/kg; s.c) and phaclofen (0, 0.5, 1, and 2 µg/rat), a GABABRs’ antagonist, were microinjected into the LHb. Their effects on firing LHb neurons were investigated using an extracellular single-unit recording in male rats.
Findings/Results: The results revealed that morphine decreased neuronal activity, and GABABRs blockade alone did not have any effect on the neuronal activity of the LHb. A low dose of the antagonist had no significant effect on neuronal firing rate, while blockade with doses of 1 and 2 µg/rat of the antagonist could significantly prevent the inhibitory effects of morphine on the LHb neuronal activity.
Conclusion and implications: This result indicated that GABABRs have a potential modulator effect, in response to morphine in the LHb.
Keywords
Full Text:
PDFReferences
Ueda H, Ueda M. Mechanisms underlying morphine analgesic tolerance and dependence. Front Biosci (Landmark Ed). 2009;14(14):5260-5272. DOI: 10.2741/3596.
Tuominen L, Tuulari J, Karlsson H, Hirvonen J, Helin S, Salminen P, et al. Aberrant mesolimbic dopamine-opiate interaction in obesity. Neuroimage. 2015;122:80-86.DOI: 10.1016/j.neuroimage.2015.08.001.
Kim J, Ham S, Hong H, Moon C, Im HI. Brain reward circuits in morphine addiction. Mol Cells. 2016;39(9):645-653.DOI: 10.14348/molcells.2016.0137.
Margolis EB, Fields HL. Mu opioid receptor actions in the lateral habenula. PloS One. 2016;11(7):e0159097,1-11.DOI: 10.1371/journal.pone.0159097.
Flanigan M, Aleyasin H, Takahashi A, Golden SA, Russo SJ. An emerging role for the lateral habenula in aggressive behavior. Pharmacol Biochem Behav. 2017;162:79-86. DOI: 10.1016/j.pbb.2017.05.003.
Bianco IH, Wilson SW. The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain. Philos Trans R Soc B Biol Sci. 2009;364(1519):1005-1020. DOI: 10.1098/rstb.2008.0213
Matsumoto M, Hikosaka O. Representation of negative motivational value in the primate lateral habenula. Nat Neurosci. 2009;12(1):77-84. DOI: 10.1038/nn.2233.
Taylor AMW, Castonguay A, Ghogha A, Vayssiere P, Pradhan AA, Xue L, et al. Neuroimmune regulation of GABAergic neurons within the ventral tegmental area during withdrawal from chronic morphine. Neuropsychopharmacology. 2016;41(4):949-959. DOI: 10.1038/npp.2015.221.
Ghamkharinejad G, Marashi SH, Foolad F, Javan M, Fathollahi Y. Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits. PloS One. 2021;16(9):e0253902,1-22.DOI: 10.1371/journal.pone.0253902
Suzuki T, Nurrochmad A, Ozaki M, Khotib J, Nakamura A, Imai S, et al. Effect of a selective GABAB receptor agonist baclofen on the μ-opioid receptor agonist-induced antinociceptive, emetic and rewarding effects. Neuropharmacology. 2005;49(8):1121-1131. DOI: 10.1016/j.neuropharm.2005.06.009.
Galaj E, Han X, Shen H, Jordan CJ, He Y, Humburg B, et al. Dissecting the role of GABA neurons in the VTA versus SNr in opioid reward. J Neurosci. 2020;40(46):8853-8869.DOI: 10.1523/JNEUROSCI.0988-20.2020.
Bouarab C, Thompson B, Polter AM. VTA GABA neurons at the interface of stress and reward. Front Neural Circuits. 2019;13:78,1-12. DOI: 10.3389/fncir.2019.00078.
Enna SJ. The GABA receptors. In: Enna SJ, Möhler H, editors. The GABA receptors: Springer; 2007. pp. 1-21. DOI: 10.1007/978-1-59745-465-0_1.
Auteri M, Zizzo MG, Serio R. GABA and GABA receptors in the gastrointestinal tract: from motility to inflammation. Pharmacol Res. 2015;93:11-21. DOI: 10.1016/j.phrs.2014.12.001.
Chebib M, Hinton T, Schmid KL, Brinkworth D, Qian H, Matos S, et al. Novel, potent, and selective GABAC antagonists inhibit myopia development and facilitate learning and memory. J Pharmacol Exp Ther. 2009;328(2):448-457. DOI: 10.1124/jpet.108.146464.
Dougherty PM, Qiao J, Wiggins R, Dafny N. Microiontophoresis of cocaine, desipramine, sulpiride, methysergide, and naloxone in habenula and parafasciculus. Exp Neurol. 1990;108(3):241-246. DOI: 10.1016/0014-4886(90)90129-G.
Hutt A. The population firing rate in the presence of GABAergic tonic inhibition in single neurons and application to general anaesthesia. Cogn Neurodyn. 2012;6(3):227-237. DOI: 10.1016/10.1007/s11571-011-9182-9.
Paladini C, Tepper J. Neurophysiology of substantia nigra dopamine neurons: modulation by GABA and glutamate. In: Steiner H, Tseng KY, editors. Handbook of behavioral neuroscience. Elsevier; 2016. pp. 335-60. DOI: 10.1016/B978-0-12-802206-1.00017-9.
Zuo W, Wang L, Chen L, Krnjević K, Fu R, Feng X, et al. Ethanol potentiates both GABAergic and glutamatergic signaling in the lateral habenula. Neuropharmacology. 2017;113(Pt A):178-187. DOI: 10.1016/j.neuropharm.2016.09.026.
Batalla A, Homberg JR, Lipina TV, Sescousse G, Luijten M, Ivanova SA, et al. The role of the habenula in the transition from reward to misery in substance use and mood disorders. Neurosci Biobehav Rev. 2017;80:276-285. DOI: 10.1016/j.neubiorev.2017.03.019.
Berkowitz BA. The relationship of pharmacokinetics to pharmacological activity: morphine, methadone and naloxone. Clin Pharmacokinet. 1976;1(3):219-230.DOI: 10.2165/00003088-197601030-00004.
Lee MR, Yu SC, Hwang BH, Chen CY. Determining morphine in biologic fluids of rats by gas chromatography–mass spectrometry. Anal Chim Acta. 2006;559(1):25-29.DOI: 10.1016/j.aca.2005.11.059.
Amohashemi E, Reisi P, Alaei H. Lateral habenula electrical stimulation with different intensities in combination with GABAB receptor antagonist reduces acquisition and expression phases of morphine-induced CPP. Neurosci Lett. 2021;759:135996,1-6. DOI: 10.1016/j.neulet.2021.135996.
Dolatabadi LK, Reisi P. Acute effect of cholecystokinin on short-term synaptic plasticity in the rat hippocampus. Res Pharm Sci. 2014;9(5):331-336.
Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 6th ed. Elsevier; 2006. pp: 57-67
Fartootzadeh R, Alaei H, Reisi P. Mutual assistance of nucleus accumbens cannabinoid receptor-1 and orexin receptor-2 in response to nicotine: a single-unit study. Res Pharm Sci. 2021;16(2):173-181.
DOI: 10.4103/1735-5362.310524.
Kowski A, Veh R, Weiss T. Dopaminergic activation excites rat lateral habenular neurons in vivo. Neuroscience. 2009;161(4):1154-1165. DOI: 10.1016/j.neuroscience.2009.04.026.
Sotty F, Danik M, Manseau F, Laplante F, Quirion R, Williams S. Distinct electrophysiological properties of glutamatergic, cholinergic and GABAergic rat septohippocampal neurons: novel implications for hippocampal rhythmicity. J Physiol. 2003;551(3):927-943. DOI: 10.1111/j.1469-7793.2003.00927.x.
Weiss T, Veh R. Morphological and electrophysiological characteristics of neurons within identified subnuclei of the lateral habenula in rat brain slices. Neuroscience. 2011;172:74-93. DOI: 10.1016/j.neuroscience.2010.10.047.
Golden SA, Heshmati M, Flanigan M, Christoffel DJ, Guise K, Pfau ML, et al. Basal forebrain projections to the lateral habenula modulate aggression reward. Nature. 2016;534(7609):688-692. DOI: 10.1038/nature18601.
Barker DJ, Miranda-Barrientos J, Zhang S, Root DH, Wang HL, Liu B, et al. Lateral preoptic control of the lateral habenula through convergent glutamate and GABA transmission. Cell Rep. 2017;21(7):1757-1769. DOI: 10.1016/j.celrep.2017.10.066.
Lecca S, Meye FJ, Mameli M. The lateral habenula in addiction and depression: an anatomical, synaptic and behavioral overview. Eur J Neurosci. 2014;39(7):1170-1178. DOI: 10.1111/ejn.12480.
Zhang L, Hernández VS, Swinny JD, Verma AK, Giesecke T, Emery AC, et al. A GABAergic cell type in the lateral habenula links hypothalamic homeostatic and midbrain motivation circuits with sex steroid signaling. Transl Psychiatry. 2018;8(1):50,1-14. DOI: 10.1038/s41398-018-0099-5.
Stamatakis AM, Stuber GD. Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance. Nat Neurosci. 2012;15(8):1105-1107. DOI: 10.1038/nn.3145.
Kim U, Chang SY. Dendritic morphology, local circuitry, and intrinsic electrophysiology of neurons in the rat medial and lateral habenular nuclei of the epithalamus. J Comp Neurol. 2005;483(2):236-250. DOI: 10.1002/cne.20410.
Meye FJ, Lecca S, Valentinova K, Mameli M. Synaptic and cellular profile of neurons in the lateral habenula. Front Hum Neurosci. 2013;7:860,1-7. DOI: 10.3389/fnhum.2013.00860.
Lecca S, Pelosi A, Tchenio A, Moutkine I, Lujan R, Hervé D, et al. Rescue of GABA B and GIRK function in the lateral habenula by protein phosphatase 2A inhibition ameliorates depression-like phenotypes in mice. Nat Med. 2016;22(3):254-261. DOI: 10.1038/nm.4037.
Lüscher C, Slesinger PA. Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease. Nat Rev Neurosci. 2010;11(5):301-315. DOI: 10.1038/nrn2834
Geisler S, Andres KH, Veh RW. Morphologic and cytochemical criteria for the identification and delineation of individual subnuclei within the lateral habenular complex of the rat. J Comp Neurol. 2003;458(1):78-97. DOI: 10.1002/cne.10566.
Lüscher C, Jan LY, Stoffel M, Malenka RC, Nicoll RA. G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. Neuron. 1997;19(3):687-695. DOI: 10.1016/S0896-6273(00)80381-5.
Good CH, Wang H, Chen YH, Mejias-Aponte CA, Hoffman AF, Lupica CR. Dopamine D4 receptor excitation of lateral habenula neurons via multiple cellular mechanisms. J Neurosci. 2013;33(43):16853-16864. DOI: 10.1523/JNEUROSCI.1844-13.2013.
Lu YG, Wang L, Chen JL, Zhu J, Meng XY, You ZD, et al. Projections from lateral habenular to tail of ventral tegmental area contribute to inhibitory effect of stress on morphine-induced conditioned place preference. Brain Res. 2019;1717:35-43. DOI: 10.1016/j.brainres.2019.03.026.
Refbacks
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.