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The GABAergic System of the Basolateral Nucleus of the Amygdaloid Complex of the Brain in Formation of Alcohol Dependence

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This review provides the first systematic report of the literature on impairments to GABAergic transmission in the basolateral nucleus of the amygdaloid complex of the brain, leading to increases in anxiety levels. Increases in anxiety are regarded as the main factor prompting alcohol cravings and producing the manifestations of alcohol dependence. Structural-functional rearrangements of ionotropic and metabotropic GABA receptors in acute and chronic exposure to ethanol and withdrawal syndrome are discussed. Data in the role of GABA transporters in the pathogenesis of alcoholism are presented.

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References

  1. I. G. Akmaev and L. B. Kalimullina, The Amygdaloid Complex of the Brain: Functional Morphology and Neuroendocrinology, Nauka, Moscow (1993).

    Google Scholar 

  2. A. V. Akhmadeev and L. B. Kalimullina, “Impairments to glutamatergic transmission in the basolateral nucleus of the amygdaloid complex on formation of alcohol dependence,” Ros. Fiziol. Zh., 102, No. 4, 385–397 (2016).

    CAS  Google Scholar 

  3. A. V. Sem’yanov, “Effects of activation of kainate receptors on tonic and phasic GABAergic inhibition in interneurons in field CA1 in hippocampal slices from guinea pigs,” Zh. Vyssh. Nerv. Deyat., 53, No. 2, 193–201 (2003).

    Google Scholar 

  4. P. V. Simonov, The Motivated Brain, Nauka, Moscow (1987).

    Google Scholar 

  5. S. A. Chepurnov and N. E. Chepurnova, The Amygdaloid Complex of the Brain, Moscow State University Press, Moscow (1981).

    Google Scholar 

  6. G. Addolorato, F. Caputo, E. Capristo, et al., “Ability of baclofen in reducing alcohol craving and intake: II-preliminary clinical evidence,” Alcohol. Clin. Exp. Res., 24, 67–71 (2000).

    CAS  PubMed  Google Scholar 

  7. G. Addolorato, F. Caputo, E. Capristo, et al., “Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study,” Alcohol Alcohol, 37, 504–508 (2002).

    Article  CAS  Google Scholar 

  8. G. Addolorato, F. Caputo, E. Capristo, et al., “Rapid suppression of alcohol withdrawal syndrome by baclofen,” Am. J. Med., 112, 226–229 (2002).

    Article  Google Scholar 

  9. G. Addolorato, L. Leggio, R. Agabio, et al., “Suppression of alcohol delirium tremens by baclofen administration: a case report,” Clin. Neuropharmacology, 26, 258–262 (2003).

    Article  Google Scholar 

  10. M. A. Avila, M. A. Real, and S. Guirado, “Patterns of GABA and GABA transporter-1 immunoreactivities in the developing and adult mouse brain amygdala,” Brain Res., 1388, 1–11 (2011).

    Article  CAS  Google Scholar 

  11. P. Barbaresi, G. Gazzanelli, and M. Malatesta, “The gamma-aminobutyric acid transporters in the cat periaqueductal gray: a light and electron microscopic immunocytochemical study,” J. Comp. Neurol., 429, No. 2, 337–354 (2001).

    Article  CAS  Google Scholar 

  12. N. P. Barrera, J. Betts, and H. You, “Atomic force microscopy reveals the stoichiometry and subunit arrangement of the alpha4beta3delta GABA(A) receptor,” Mol. Pharmacol., 73, No. 3, 960–967 (2008).

    Article  CAS  Google Scholar 

  13. B. Bettler, K. Kaupmann, and N. G. Bowery, “GABAb receptors: Drugs meet clones,” Curr. Opin. Neurobiol., 8, 345–350 (1998).

    Article  CAS  Google Scholar 

  14. B. Bettler, K. Kaupmann, J. Mosbacher, and M. Gassmann, “Molecular structure and physiological functions of GABAB receptors,” Physiol. Rev., 84, 835–867 (2004).

    Article  CAS  Google Scholar 

  15. S. Bischoff, S. Leonhard, N. Reymann, et al., “Spatial distribution of GABABR1 receptor mRNA and binding sites in the rat brain,” J. Comp. Neurol., 412, 1–16 (1999).

    Article  CAS  Google Scholar 

  16. G. Bonanno, A. Fassio, G. Schmid, et al., “Pharmacologically distinct GABAB receptors that mediate inhibition of GABA and glutamate release in human neocortex,” Br. J. Pharmacol., 120, 60–64 (1997).

    Article  CAS  Google Scholar 

  17. J. Bormann, “The ‘ABC’ of GABA receptors,” Trends Pharmacol. Sci., 21, No. 1, 16–19 (2000).

    Article  CAS  Google Scholar 

  18. N. G. Bowery, D. R. Hill, A. L. Hudson, et al., “Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor,” Nature, 283, 92–94 (1980).

    Article  CAS  Google Scholar 

  19. N. G. Bowery, A. L. Hudson, and G. W. Price, “GABAA and GABAB receptor site distribution in the rat central nervous system,” Neuroscience, 20, 365–383 (1987).

    Article  CAS  Google Scholar 

  20. K. Brebner, R. Phelan, and D. C. Roberts, “Effect of baclofen on cocaine self-administration in rats reinforced under fixed-ratio 1 and progressive-ratio schedules,” Psychopharmacology, 148, 314–321 (2000).

    Article  CAS  Google Scholar 

  21. A. Caitlin, A. Orsini, and S. Maren, “Neural and cellular mechanisms of fear and extinction memory formation,” Neurosci. Biobehav. Rev., 36, No. 7, 1773–1802 (2012).

    Article  Google Scholar 

  22. L. L. Devaud, “Ethanol dependence has limited effects on GABA or glutamate transporters in rat brain,” Alcohol Clin. Exp. Res., 25, No. 4, 606–611 (2001).

    Article  CAS  Google Scholar 

  23. M. R. Diaz, D. T. Christian, N. J. Anderson, and B. A. McCoo, “Chronic ethanol and withdrawal differentially modulate lateral/basolateral amygdala paracapsular and local GABAergic synapses,” J. Pharmacol. Exp. Ther., 337, No. 1, 162–170 (2011), DOI: https://doi.org/10.1124/jpet.110.177121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. P. Fadda, M. Scherma, A. Fresu, et al., “Baclofen antagonizes nicotine-, cocaine-, and morphine-induced dopamine release in the nucleus accumbens of rat,” Synapse, 50, 1–6 (2003).

    Article  CAS  Google Scholar 

  25. M. Filip and M. Frankowska, “GABA(B) receptors in drug addiction,” Pharmacol. Rep., 60, No. 6, 755–770 (2008).

    CAS  PubMed  Google Scholar 

  26. D. W. Floyd, D. P. Friedman, and J. B. Daunais, “Long-term ethanol self-administration by cynomolgus macaques alters the pharmacology and expression of GABAA receptors in basolateral amygdala,” J. Pharmacol. Exp. Ther., 311, No. 3, 1071–1079 (2004).

    Article  CAS  Google Scholar 

  27. J. Fujimura, M. Nagano, and H. Suzuki, “Differential expression of GABA(A) receptor subunits in the distinct nuclei of rat amygdala,” Brain Res. Mol. Brain Res., 138, No. 1, 17–23 (2005).

    Article  CAS  Google Scholar 

  28. A. Gadea and A. M. Lopez-Colome, “Glial transporters for glutamate, glycine, and GABA: II. GABA transporters,” J. Neurosci. Res., 63, No. 6, 461–468 (2001).

    Article  CAS  Google Scholar 

  29. S. A. Heldt and Ressler K. J. “Training-induced changes in the expression of GABAA-associated genes in the amygdala after the acquisition and extinction of Pavlovian fear,” Eur. J. Neurosci., 26, No. 12, 3631–3644 (2007).

    Article  Google Scholar 

  30. J. H. Hu, Y. H. Ma, and N. Yang, “Up-regulation of gamma-aminobutyric acid transporter I mediates ethanol sensitivity in mice,” Neuroscience, 123, No. 4, 807–812 (2004).

    Article  CAS  Google Scholar 

  31. A. S. Hwang and G. L. Wilcox, “Baclofen, gamma-aminobutyric acid B receptors and substance P in the mouse spinal cord,” J. Pharmacol. Exp. Ther., 248, 1026–1033 (1989).

    CAS  PubMed  Google Scholar 

  32. Y. Ikarashi, M. Yuzurihara, A. Takahashi, et al., “Modulation of acetylcholine release via GABAA and GABAB receptors in rat striatum,” Brain Res., 816, 238–240 (1999).

    Article  Google Scholar 

  33. R. Imperatore, G. Morello, and L. Luongo, “Genetic deletion of monoacylglycerol lipase leads to impaired cannabinoid receptor CB1R signaling and anxiety-like behavior,” J. Neurochem., 135, No. 4, 799–813 (2015), DOI: https://doi.org/10.1111/jnc.13267.

    Article  CAS  PubMed  Google Scholar 

  34. J. H. Jennings, D. R. Sparta, A. M. Stamatakis, et al., “Distinct extended amygdala circuits for divergent motivational states,” Nature, 496, 224–228 (2013).

    Article  CAS  Google Scholar 

  35. F. Jursky, S. Tamura, and A. Tamura, “Structure, function and brain localization of neurotransmitter transporters,” J. Exp. Biol., 196, 283–295 (1994).

    CAS  PubMed  Google Scholar 

  36. K. Kaupmann, B. Malitschek, V. Schuler, et al., “GABAB-receptor subtypes assemble into functional heteromeric complexes,” Nature, 396, 683–687 (1998).

    Article  CAS  Google Scholar 

  37. D. I. Kerr and J. Ong, “GABAB receptors,” Pharmacol. Ther., 67, 187–246 (1995).

    Article  CAS  Google Scholar 

  38. M. A. Klitenick, P. DeWitte, and P. W. Kalivas, “Regulation of somatodendritic dopamine release I the ventral tegmental area by opioids and GABA: an in vivo microdialysis study,” J. Neurosci., 12, 2623–2632 (1992).

    Article  CAS  Google Scholar 

  39. D. J. Knapp, D. H. Overstreet, and G. R. Breese, “Baclofen blocks expression and sensitization of anxiety-like behavior in an animal model of repeated stress and ethanol withdrawal,” Alcohol. Clin. Exp. Res., 31, 582–595 (2007).

    Article  CAS  Google Scholar 

  40. G. F. Koob, “Negative reinforcement in drug addiction: the darkness within,” Curr. Opin. Neurobiol., 23, 559–563 (2013), DOI: https://doi.org/10.1016/j.conb.2013.03.011.

    Article  CAS  PubMed  Google Scholar 

  41. P. Koulen, B. Malitschek, R. Kuhn, et al., “Presynaptic and postsynaptic localization of GABAB receptors in neurons of the rat retina,” Eur. J. Neurosci., 10, 1446–1456 (1998).

    Article  CAS  Google Scholar 

  42. J. H. Liang, F. Chen, E. Krstew, et al., “The GABAb receptor allosteric modulator CGP7930, like baclofen, reduces operant self-administration of ethanol in alcohol preferring rats,” Neuropharmacology, 50, 632–639 (2006).

    Article  CAS  Google Scholar 

  43. F. Liang, Y. Hatanaka, H. Saito, et al., “Differential expression of aminobutyric acid type B receptor-1a and -1b mRNA variants in GABA and nonGABAergic neurons of the rat brain,” J. Comp. Neurol., 416, 475–495 (2000).

    Article  CAS  Google Scholar 

  44. A. K. Lindemeyer, J. Liang, and V. N. Marty, “Ethanol-induced plasticity of GABAA receptors in basolateral amygdala,” Neurochem. Res., 39, No. 6, 1162–1170 (2014), DOI: https://doi.org/10.1007/s11064-014-1297-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. N. J. Mabjeesh, M. Frese, T. Rauen, et al., “Neuronal and glial gamma-aminobutyric acid+ transporters are distinct proteins,” FEBS Lett., 299, 99–102 (1992).

    Article  CAS  Google Scholar 

  46. P. Maccioni, D. Pes, A. Orru, et al., “Reducing effect of the positive allosteric modulator of the GABAB receptor, GS39,783, on alcohol self-administration in alcohol-preferring rats,” Psychopharmacology, 193, 171–178 (2007).

    Article  CAS  Google Scholar 

  47. A. Marowsky, J. M. Fritschy, and K. E. Vogt, “Functional mapping of GABAA receptor subtypes in the amygdala,” Eur. J. Neurosci., 20, No. 5, 1281–1289 (2004).

    Article  Google Scholar 

  48. F. Mascagni, E. C. Muly, D. G. Rainnie, and A. J. McDonald, “Immunohistochemical characterization of parvalbumin-containing interneurons in the monkey basolateral amygdala,” Neuroscience, 158, No. 4, 1541–1550 (2009).

    Article  CAS  Google Scholar 

  49. A. J. McDonald and J. L. Culberson, “Efferent projection of the basolateral amygdala in opossum, Didelphis virginiana,” Brain Res. Bull., 17, No. 3, 335–350 (1986).

    Article  CAS  Google Scholar 

  50. A. J. McDonald and F. Mascagni, “Parvalbumin-containing interneurons in the basolateral amygdala express high levels of the alpha1 subunit of GABAA receptor,” J. Comp. Neurol., 473, No. 1, 137–146 (2004).

    Article  CAS  Google Scholar 

  51. A. J. McDonald, J. F. Muller, and F. Mascagni, “Postsynaptic targets of GABAergic basal forebrain projection to the basolateral amygdala,” Neuroscience, 183, 144–159 (2011), DOI: https://doi.org/10.1016/j.neuroscience.2011.03.027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. A. Minelli, N. C. Brecha, and C. Karschin, “GAT-1, a high-affinity GABA plasma membrane transporter, is localized to neurons and glia in cerebral cortex,” J. Neurosci., 15, No. 11, 7734–7746 (1995).

    Article  CAS  Google Scholar 

  53. J. F. Muller, F. Mascagni, and A. J. McDonald, “Pyramidal cells of the rat basolateral amygdala synaptology and innervations by parvalbumin-immunoreactive interneurons,” J. Comp. Neurol., 494, No. 4, 635–650 (2006).

    Article  Google Scholar 

  54. N. Nayeem, T. P. Green, I. L. Martin, and E. A. Barnard, “Quaternary structure of the native GABAA receptor determined by electron microscopic image analysis,” J. Neurochem., 62, No. 2, 815–818 (1994).

    Article  CAS  Google Scholar 

  55. A. Orru, P. Lai, C. Lobina, et al., “Reducing effect of the positive allosteric modulators of the GABAB receptor, CGP7930 and GS39783, on alcohol intake in alcohol-preferring rats,” Eur. J. Pharmacol., 525, 105–111 (2005).

    Article  CAS  Google Scholar 

  56. N. E. Paterson, S. Vlachou, S. Query, et al., “Positive modulation of GABAB receptors decreased nicotine self-administration and counteracted nicotine-induced enhancement of brain reward function in rats,” J. Pharmacol. Exp. Ther., 326, 306–314 (2008).

    Article  CAS  Google Scholar 

  57. C. R. Pinard, J. F. Muller, F. Mascagni, and A. J. McDonald, “Dopaminergic innervation of interneurons in the rat basolateral amygdala,” Neuroscience, 157, No. 4, 850–863 (2008).

    Article  CAS  Google Scholar 

  58. A. P. Princivalle, M. N. Pangalos, N. G. Bowery, and R. Spreafico, “Distribution of GA-BABla, GABABlb and GABAB2 receptor protein in cerebral cortex and thalamus of adult rats,” Neuroreport, 12, 591–595 (2001).

    Article  CAS  Google Scholar 

  59. R. Radian, O. P. Ottersen, J. Storm-Mathisen, et al., “Immunocytochemical localization of the GABA transporter in rat brain,” J. Neurosci., 10, 1319–1330 (1990).

    Article  CAS  Google Scholar 

  60. P. S. Rao, R. L. Bell, E. A. Engleman, and Y. Sar, “Targeting glutamate uptake to treat alcohol use disorders,” Front. Neurosci., 9, 144–149 (2015).

    Article  CAS  Google Scholar 

  61. A. Sarup, O. M. Larsson, and A. Schousboe, “GABA transporters and GABA-transaminase as drug targets,” Curr. Drug Targets CNS Neurol. Disord., 2, No. 4, 269–277 (2003).

    Article  CAS  Google Scholar 

  62. A. Schousboe, A. Sarup, O. M. Larsson, and H. S. White, “GABA transporters as drug targets for modulation of GABAergic activity,” Biochem. Pharmacol., 68, No. 8, 1557–1563 (2004).

    Article  CAS  Google Scholar 

  63. Y. Silberman, O. J. Ariwodola, and J. L. Weiner, “Differential effect of GABAB autoreceptor activation on ethanol potentiation of local and lateral paracapsular GABAergic synapses in the rat basolateral amygdala,” Neuropharmacology, 56, No. 5, 886–895 (2009), DOI: https://doi.org/10.1016/j.neuropharm.2009.01.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. J. Spampanato, J. Polepalli, and P. Sah, “Interneurons in the basolateral amygdala,” Neuropharmacology, 60, No. 5, 765–773 (2011).

    Article  CAS  Google Scholar 

  65. B. H. Westerink, H. F. Kwint, and J. B. de Vries, “Eating-induced dopamine release from mesolimbic neurons is mediated by NMDA receptors in the ventral tegmental area: a dual-probe microdialysis study,” J. Neurochem., 69, 662–668 (1997).

    Article  CAS  Google Scholar 

  66. D. Wirtshafter and A. C. Sheppard, “Localization of GABAB receptors in midbrain monoamine containing neurons in the rat,” Brain Res. Bull., 56, 1–5 (2001).

    Article  CAS  Google Scholar 

  67. Z. X. Xi and E. A. Stein, “Baclofen inhibits heroin self-administration behavior and mesolimbic dopamine release,” J. Pharmacol. Exp. Ther., 290, 1369–1374 (1999).

    CAS  PubMed  Google Scholar 

  68. M. Yoshida, H. Yokoo, T. Tanaka, et al., “Opposite changes in the mesolimbic dopamine metabolism in the nerve terminal and cell body sites induced by locally infused baclofen in the rat,” Brain Res., 636, 111–114 (1994).

    Article  CAS  Google Scholar 

  69. L. Zhu, “Ethanol potentiates GABAergic synaptic transmission in a postsynaptic neuron/synaptic bouton preparation from basolateral amygdala,” J. Neurophysiol., 96, No. 1, 433–441 (2006).

    Article  Google Scholar 

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  1. Bashkir State University, Ufa, Russia

    A. V. Akhmadeev & L. B. Kalimullina

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Correspondence to A. V. Akhmadeev.

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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 103, No. 9, pp. 978–986, September, 2017.

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Akhmadeev, A.V., Kalimullina, L.B. The GABAergic System of the Basolateral Nucleus of the Amygdaloid Complex of the Brain in Formation of Alcohol Dependence. Neurosci Behav Physi 49, 463–467 (2019). https://doi.org/10.1007/s11055-019-00756-6

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