Increased dopaminergic neurotransmission results in ethanol dependent sedative behaviors in Caenorhabditis elegans

Autoři: Pratima Pandey aff001;  Anuradha Singh aff001;  Harjot Kaur aff002;  Anindya Ghosh-Roy aff002;  Kavita Babu aff001
Působiště autorů: Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Mohali, India aff001;  National Brain Research Centre, Gurgaon, India aff002;  Centre for Neuroscience, Indian Institute of Science (IISc), Bangalore, India aff003
Vyšlo v časopise: Increased dopaminergic neurotransmission results in ethanol dependent sedative behaviors in Caenorhabditis elegans. PLoS Genet 17(2): e1009346. doi:10.1371/journal.pgen.1009346
Kategorie: Research Article


Ethanol is a widely used drug, excessive consumption of which could lead to medical conditions with diverse symptoms. Ethanol abuse causes dysfunction of memory, attention, speech and locomotion across species. Dopamine signaling plays an essential role in ethanol dependent behaviors in animals ranging from C. elegans to humans. We devised an ethanol dependent assay in which mutants in the dopamine autoreceptor, dop-2, displayed a unique sedative locomotory behavior causing the animals to move in circles while dragging the posterior half of their body. Here, we identify the posterior dopaminergic sensory neuron as being essential to modulate this behavior. We further demonstrate that in dop-2 mutants, ethanol exposure increases dopamine secretion and functions in a DVA interneuron dependent manner. DVA releases the neuropeptide NLP-12 that is known to function through cholinergic motor neurons and affect movement. Thus, DOP-2 modulates dopamine levels at the synapse and regulates alcohol induced movement through NLP-12.

Klíčová slova:

Animal behavior – Behavior – Biological locomotion – Caenorhabditis elegans – Dopamine – Graphs – Motor neurons – Neurons


1. Prescott CA, Kendler KS. Genetic and environmental contributions to alcohol abuse and dependence in a population-based sample of male twins. Am J Psychiatry. 1999;156(1):34–40. doi: 10.1176/ajp.156.1.34 9892295.

2. Schuckit MA, Smith TL. An 8-year follow-up of 450 sons of alcoholic and control subjects. Arch Gen Psychiatry. 1996;53(3):202–10. doi: 10.1001/archpsyc.1996.01830030020005 8611056.

3. Bettinger JC, Davies AG. The role of the BK channel in ethanol response behaviors: evidence from model organism and human studies. Front Physiol. 2014;5:346. doi: 10.3389/fphys.2014.00346 25249984; PubMed Central PMCID: PMC4158801.

4. Harris RA, Trudell JR, Mihic SJ. Ethanol's molecular targets. Sci Signal. 2008;1(28):re7. doi: 10.1126/scisignal.128re7 18632551; PubMed Central PMCID: PMC2671803.

5. Spanagel R. Alcoholism: a systems approach from molecular physiology to addictive behavior. Physiol Rev. 2009;89(2):649–705. doi: 10.1152/physrev.00013.2008 19342616.

6. Baik JH. Dopamine signaling in reward-related behaviors. Front Neural Circuits. 2013;7:152. doi: 10.3389/fncir.2013.00152 24130517; PubMed Central PMCID: PMC3795306.

7. Strader CD, Fong TM, Tota MR, Underwood D, Dixon RA. Structure and function of G protein-coupled receptors. Annu Rev Biochem. 1994;63:101–32. Epub 1994/01/01. doi: 10.1146/ 7979235.

8. Zhou QY, Grandy DK, Thambi L, Kushner JA, Van Tol HH, Cone R, et al. Cloning and expression of human and rat D1 dopamine receptors. Nature. 1990;347(6288):76–80. doi: 10.1038/347076a0 2168520.

9. Bunzow JR, Van Tol HH, Grandy DK, Albert P, Salon J, Christie M, et al. Cloning and expression of a rat D2 dopamine receptor cDNA. Nature. 1988;336(6201):783–7. doi: 10.1038/336783a0 2974511.

10. Pandey P, Harbinder S. The Caenorhabditis elegans D2-like dopamine receptor DOP-2 physically interacts with GPA-14, a Galphai subunit. J Mol Signal. 2012;7(1):3. doi: 10.1186/1750-2187-7-3 22280843; PubMed Central PMCID: PMC3297496.

11. Ford CP. The role of D2-autoreceptors in regulating dopamine neuron activity and transmission. Neuroscience. 2014;282:13–22. doi: 10.1016/j.neuroscience.2014.01.025 24463000; PubMed Central PMCID: PMC4108583.

12. Rivet JM, Audinot V, Gobert A, Peglion JL, Millan MJ. Modulation of mesolimbic dopamine release by the selective dopamine D3 receptor antagonist, (+)-S 14297. Eur J Pharmacol. 1994;265(3):175–7. doi: 10.1016/0014-2999(94)90429-4 7875234.

13. Koeltzow TE, Xu M, Cooper DC, Hu XT, Tonegawa S, Wolf ME, et al. Alterations in dopamine release but not dopamine autoreceptor function in dopamine D3 receptor mutant mice. J Neurosci. 1998;18(6):2231–8. doi: 10.1523/JNEUROSCI.18-06-02231.1998 9482807.

14. Beaulieu JM, Gainetdinov RR. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev. 2011;63(1):182–217. doi: 10.1124/pr.110.002642 21303898.

15. Lu RB, Lee JF, Ko HC, Lin WW. Dopamine D2 receptor gene (DRD2) is associated with alcoholism with conduct disorder. Alcohol Clin Exp Res. 2001;25(2):177–84. 11236830.

16. Thanos PK, Rivera SN, Weaver K, Grandy DK, Rubinstein M, Umegaki H, et al. Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking. Life Sci. 2005;77(2):130–9. doi: 10.1016/j.lfs.2004.10.061 15862598.

17. Volkow ND, Wang GJ, Begleiter H, Porjesz B, Fowler JS, Telang F, et al. High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors. Arch Gen Psychiatry. 2006;63(9):999–1008. Epub 2006/09/06. doi: 10.1001/archpsyc.63.9.999 16953002.

18. Kraschewski A, Reese J, Anghelescu I, Winterer G, Schmidt LG, Gallinat J, et al. Association of the dopamine D2 receptor gene with alcohol dependence: haplotypes and subgroups of alcoholics as key factors for understanding receptor function. Pharmacogenet Genomics. 2009;19(7):513–27. Epub 2009/07/16. doi: 10.1097/fpc.0b013e32832d7fd3 19603545.

19. Volkow ND, Tomasi D, Wang GJ, Telang F, Fowler JS, Logan J, et al. Predominance of D2 receptors in mediating dopamine's effects in brain metabolism: effects of alcoholism. J Neurosci. 2013;33(10):4527–35. Epub 2013/03/08. doi: 10.1523/JNEUROSCI.5261-12.2013 23467368; PubMed Central PMCID: PMC3732804.

20. Feltmann K, Borroto-Escuela DO, Ruegg J, Pinton L, de Oliveira Sergio T, Narvaez M, et al. Effects of Long-Term Alcohol Drinking on the Dopamine D2 Receptor: Gene Expression and Heteroreceptor Complexes in the Striatum in Rats. Alcohol Clin Exp Res. 2018;42(2):338–51. Epub 2017/12/06. doi: 10.1111/acer.13568 29205397; PubMed Central PMCID: PMC5817245.

21. Corsi AK, Wightman B, Chalfie M. A Transparent Window into Biology: A Primer on Caenorhabditis elegans. Genetics. 2015;200(2):387–407. doi: 10.1534/genetics.115.176099 26088431; PubMed Central PMCID: PMC4492366.

22. Schafer WR. Addiction research in a simple animal model: the nematode Caenorhabditis elegans. Neuropharmacology. 2004;47 Suppl 1:123–31. doi: 10.1016/j.neuropharm.2004.06.026 15464131.

23. Giacomotto J, Segalat L. High-throughput screening and small animal models, where are we? Br J Pharmacol. 2010;160(2):204–16. doi: 10.1111/j.1476-5381.2010.00725.x 20423335; PubMed Central PMCID: PMC2874843.

24. Alaimo JT, Davis SJ, Song SS, Burnette CR, Grotewiel M, Shelton KL, et al. Ethanol metabolism and osmolarity modify behavioral responses to ethanol in C. elegans. Alcohol Clin Exp Res. 2012;36(11):1840–50. doi: 10.1111/j.1530-0277.2012.01799.x 22486589; PubMed Central PMCID: PMC3396773.

25. Hawkins EG, Martin I, Kondo LM, Judy ME, Brings VE, Chan CL, et al. A novel cholinergic action of alcohol and the development of tolerance to that effect in Caenorhabditis elegans. Genetics. 2015;199(1):135–49. doi: 10.1534/genetics.114.171884 25342716; PubMed Central PMCID: PMC4286678.

26. Bettinger JC, Carnell L, Davies AG, McIntire SL. The use of Caenorhabditis elegans in molecular neuropharmacology. Int Rev Neurobiol. 2004;62:195–212. doi: 10.1016/S0074-7742(04)62007-1 15530573.

27. Sulston J, Dew M, Brenner S. Dopaminergic neurons in the nematode Caenorhabditis elegans. J Comp Neurol. 1975;163(2):215–26. doi: 10.1002/cne.901630207 240872.

28. Hegarty SV, Sullivan AM, O'Keeffe GW. Midbrain dopaminergic neurons: a review of the molecular circuitry that regulates their development. Dev Biol. 2013;379(2):123–38. doi: 10.1016/j.ydbio.2013.04.014 23603197.

29. Suo S, Sasagawa N, Ishiura S. Cloning and characterization of a Caenorhabditis elegans D2-like dopamine receptor. J Neurochem. 2003;86(4):869–78. doi: 10.1046/j.1471-4159.2003.01896.x 12887685.

30. Suo S, Sasagawa N, Ishiura S. Identification of a dopamine receptor from Caenorhabditis elegans. Neurosci Lett. 2002;319(1):13–6. doi: 10.1016/s0304-3940(01)02477-6 11814642.

31. Davies AG, Pierce-Shimomura JT, Kim H, VanHoven MK, Thiele TR, Bonci A, et al. A central role of the BK potassium channel in behavioral responses to ethanol in C. elegans. Cell. 2003;115(6):655–66. doi: 10.1016/s0092-8674(03)00979-6 14675531.

32. Lee J, Jee C, McIntire SL. Ethanol preference in C. elegans. Genes Brain Behav. 2009;8(6):578–85. doi: 10.1111/j.1601-183X.2009.00513.x 19614755; PubMed Central PMCID: PMC2880621.

33. Correa PA, Gruninger T, Garcia LR. DOP-2 D2-Like Receptor Regulates UNC-7 Innexins to Attenuate Recurrent Sensory Motor Neurons during C. elegans Copulation. J Neurosci. 2015;35(27):9990–10004. doi: 10.1523/JNEUROSCI.0940-15.2015 26156999; PubMed Central PMCID: PMC4495247.

34. Voglis G, Tavernarakis N. A synaptic DEG/ENaC ion channel mediates learning in C. elegans by facilitating dopamine signalling. EMBO J. 2008;27(24):3288–99. doi: 10.1038/emboj.2008.252 19037257; PubMed Central PMCID: PMC2609744.

35. Correa P, LeBoeuf B, Garcia LR. C. elegans dopaminergic D2-like receptors delimit recurrent cholinergic-mediated motor programs during a goal-oriented behavior. PLoS Genet. 2012;8(11):e1003015. doi: 10.1371/journal.pgen.1003015 23166505; PubMed Central PMCID: PMC3499252.

36. Suo S, Culotti JG, Van Tol HH. Dopamine counteracts octopamine signalling in a neural circuit mediating food response in C. elegans. EMBO J. 2009;28(16):2437–48. doi: 10.1038/emboj.2009.194 19609300; PubMed Central PMCID: PMC2735167.

37. Hu Z, Pym EC, Babu K, Vashlishan Murray AB, Kaplan JM. A neuropeptide-mediated stretch response links muscle contraction to changes in neurotransmitter release. Neuron. 2011;71(1):92–102. Epub 2011/07/13. S0896-6273(11)00377-1 [pii] doi: 10.1016/j.neuron.2011.04.021 21745640; PubMed Central PMCID: PMC3134788.

38. Bhattacharya R, Touroutine D, Barbagallo B, Climer J, Lambert CM, Clark CM, et al. A conserved dopamine-cholecystokinin signaling pathway shapes context-dependent Caenorhabditis elegans behavior. PLoS Genet. 2014;10(8):e1004584. doi: 10.1371/journal.pgen.1004584 25167143; PubMed Central PMCID: PMC4148232.

39. Sawin ER, Ranganathan R, Horvitz HR. C. elegans locomotory rate is modulated by the environment through a dopaminergic pathway and by experience through a serotonergic pathway. Neuron. 2000;26(3):619–31. doi: 10.1016/s0896-6273(00)81199-x 10896158.

40. McDonald PW, Jessen T, Field JR, Blakely RD. Dopamine signaling architecture in Caenorhabditis elegans. Cell Mol Neurobiol. 2006;26(4–6):593–618. doi: 10.1007/s10571-006-9003-6 16724276.

41. Allen AT, Maher KN, Wani KA, Betts KE, Chase DL. Coexpressed D1- and D2-like dopamine receptors antagonistically modulate acetylcholine release in Caenorhabditis elegans. Genetics. 2011;188(3):579–90. doi: 10.1534/genetics.111.128512 21515580; PubMed Central PMCID: PMC3176529.

42. Chase DL, Pepper JS, Koelle MR. Mechanism of extrasynaptic dopamine signaling in Caenorhabditis elegans. Nat Neurosci. 2004;7(10):1096–103. doi: 10.1038/nn1316 15378064.

43. Suo S, Ishiura S. Dopamine modulates acetylcholine release via octopamine and CREB signaling in Caenorhabditis elegans. PloS one. 2013;8(8):e72578. doi: 10.1371/journal.pone.0072578 23977320; PubMed Central PMCID: PMC3745381.

44. Kameda SR, Frussa-Filho R, Carvalho RC, Takatsu-Coleman AL, Ricardo VP, Patti CL, et al. Dissociation of the effects of ethanol on memory, anxiety, and motor behavior in mice tested in the plus-maze discriminative avoidance task. Psychopharmacology (Berl). 2007;192(1):39–48. doi: 10.1007/s00213-006-0684-9 17242924.

45. Siciliano CA, Mauterer MI, Fordahl SC, Jones SR. Modulation of striatal dopamine dynamics by cocaine self-administration and amphetamine treatment in female rats. Eur J Neurosci. 2019. doi: 10.1111/ejn.14437 31111573.

46. Davies AG, McIntire SL. Using C. elegans to screen for targets of ethanol and behavior-altering drugs. Biol Proced Online. 2004;6:113–9. doi: 10.1251/bpo79 15192754; PubMed Central PMCID: PMC420456.

47. Weinshenker D, Garriga G, Thomas JH. Genetic and pharmacological analysis of neurotransmitters controlling egg laying in C. elegans. J Neurosci. 1995;15(10):6975–85. Epub 1995/10/01. doi: 10.1523/JNEUROSCI.15-10-06975.1995 7472454; PubMed Central PMCID: PMC6577982.

48. Ishita Y, Chihara T, Okumura M. Serotonergic modulation of feeding behavior in Caenorhabditis elegans and other related nematodes. Neurosci Res. 2020;154:9–19. Epub 2019/04/28. doi: 10.1016/j.neures.2019.04.006 31028772.

49. Vidal-Gadea AG, Pierce-Shimomura JT. Conserved role of dopamine in the modulation of behavior. Commun Integr Biol. 2012;5(5):440–7. Epub 2012/11/28. doi: 10.4161/cib.20978 23181157; PubMed Central PMCID: PMC3502204.

50. Li W, Kang L, Piggott BJ, Feng Z, Xu XZ. The neural circuits and sensory channels mediating harsh touch sensation in Caenorhabditis elegans. Nat Commun. 2011;2:315. doi: 10.1038/ncomms1308 21587232; PubMed Central PMCID: PMC3098610.

51. Bhattacharya R, Francis MM. In the proper context: Neuropeptide regulation of behavioral transitions during food searching. Worm. 2015;4(3):e1062971. doi: 10.1080/21624054.2015.1062971 26430569; PubMed Central PMCID: PMC4588156.

52. Jansen G, Thijssen KL, Werner P, van der Horst M, Hazendonk E, Plasterk RH. The complete family of genes encoding G proteins of Caenorhabditis elegans. Nat Genet. 1999;21(4):414–9. doi: 10.1038/7753 10192394.

53. Omura DT, Clark DA, Samuel AD, Horvitz HR. Dopamine signaling is essential for precise rates of locomotion by C. elegans. PloS one. 2012;7(6):e38649. doi: 10.1371/journal.pone.0038649 22719914; PubMed Central PMCID: PMC3374838.

54. Benoit-Marand M, Borrelli E, Gonon F. Inhibition of dopamine release via presynaptic D2 receptors: time course and functional characteristics in vivo. J Neurosci. 2001;21(23):9134–41. doi: 10.1523/JNEUROSCI.21-23-09134.2001 11717346.

55. Rouge-Pont F, Usiello A, Benoit-Marand M, Gonon F, Piazza PV, Borrelli E. Changes in extracellular dopamine induced by morphine and cocaine: crucial control by D2 receptors. J Neurosci. 2002;22(8):3293–301. doi: 20026322 11943831.

56. Schmitz Y, Schmauss C, Sulzer D. Altered dopamine release and uptake kinetics in mice lacking D2 receptors. J Neurosci. 2002;22(18):8002–9. doi: 10.1523/JNEUROSCI.22-18-08002.2002 12223553.

57. Samuel AD, Silva RA, Murthy VN. Synaptic activity of the AFD neuron in Caenorhabditis elegans correlates with thermotactic memory. J Neurosci. 2003;23(2):373–6. doi: 10.1523/JNEUROSCI.23-02-00373.2003 12533596.

58. Miesenbock G, De Angelis DA, Rothman JE. Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature. 1998;394(6689):192–5. doi: 10.1038/28190 9671304.

59. Formisano R, Mersha MD, Caplan J, Singh A, Rankin CH, Tavernarakis N, et al. Synaptic vesicle fusion is modulated through feedback inhibition by dopamine auto-receptors. Synapse. 2020;74(1):e22131. doi: 10.1002/syn.22131 31494966.

60. Hardaway JA, Sturgeon SM, Snarrenberg CL, Li Z, Xu XZ, Bermingham DP, et al. Glial Expression of the Caenorhabditis elegans Gene swip-10 Supports Glutamate Dependent Control of Extrasynaptic Dopamine Signaling. J Neurosci. 2015;35(25):9409–23. doi: 10.1523/JNEUROSCI.0800-15.2015 26109664; PubMed Central PMCID: PMC4478255.

61. Lee FJ, Pei L, Moszczynska A, Vukusic B, Fletcher PJ, Liu F. Dopamine transporter cell surface localization facilitated by a direct interaction with the dopamine D2 receptor. EMBO J. 2007;26(8):2127–36. Epub 2007/03/24. doi: 10.1038/sj.emboj.7601656 17380124; PubMed Central PMCID: PMC1852782.

62. Carvelli L, McDonald PW, Blakely RD, DeFelice LJ. Dopamine transporters depolarize neurons by a channel mechanism. Proc Natl Acad Sci U S A. 2004;101(45):16046–51. doi: 10.1073/pnas.0403299101 15520385; PubMed Central PMCID: PMC528740.

63. Janssen T, Meelkop E, Lindemans M, Verstraelen K, Husson SJ, Temmerman L, et al. Discovery of a cholecystokinin-gastrin-like signaling system in nematodes. Endocrinology. 2008;149(6):2826–39. doi: 10.1210/en.2007-1772 18339709.

64. Peeters L, Janssen T, De Haes W, Beets I, Meelkop E, Grant W, et al. A pharmacological study of NLP-12 neuropeptide signaling in free-living and parasitic nematodes. Peptides. 2012;34(1):82–7. doi: 10.1016/j.peptides.2011.10.014 22019590.

65. Tao L, Porto D, Li Z, Fechner S, Lee SA, Goodman MB, et al. Parallel Processing of Two Mechanosensory Modalities by a Single Neuron in C. elegans. Dev Cell. 2019;51(5):617–31 e3. doi: 10.1016/j.devcel.2019.10.008 31735664.

66. Hums I, Riedl J, Mende F, Kato S, Kaplan HS, Latham R, et al. Regulation of two motor patterns enables the gradual adjustment of locomotion strategy in Caenorhabditis elegans. Elife. 2016;5. doi: 10.7554/eLife.14116 27222228; PubMed Central PMCID: PMC4880447.

67. Oranth A, Schultheis C, Tolstenkov O, Erbguth K, Nagpal J, Hain D, et al. Food Sensation Modulates Locomotion by Dopamine and Neuropeptide Signaling in a Distributed Neuronal Network. Neuron. 2018;100(6):1414–28 e10. doi: 10.1016/j.neuron.2018.10.024 30392795.

68. Ramachandran S, Banerjee N, Bhattacharya R, Touroutine D, Lambert CM, Schoofs L, et al. A conserved neuropeptide system links head and body motor circuits to enable adaptive behavior. bioRxiv. 2020. Epub April 28, 2020.

69. Gray JM, Hill JJ, Bargmann CI. A circuit for navigation in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2005;102(9):3184–91. doi: 10.1073/pnas.0409009101 15689400; PubMed Central PMCID: PMC546636.

70. Li W, Feng Z, Sternberg PW, Xu XZ. A C. elegans stretch receptor neuron revealed by a mechanosensitive TRP channel homologue. Nature. 2006;440(7084):684–7. doi: 10.1038/nature04538 16572173; PubMed Central PMCID: PMC2865900.

71. Rand JB, Russell RL. Choline acetyltransferase-deficient mutants of the nematode Caenorhabditis elegans. Genetics. 1984;106(2):227–48. 6698395; PubMed Central PMCID: PMC1202253.

72. Touroutine D, Fox RM, Von Stetina SE, Burdina A, Miller DM, 3rd, Richmond JE. acr-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the Caenorhabditis elegans neuromuscular junction. J Biol Chem. 2005;280(29):27013–21. doi: 10.1074/jbc.M502818200 15917232.

73. Babu K, Hu Z, Chien SC, Garriga G, Kaplan JM. The immunoglobulin super family protein RIG-3 prevents synaptic potentiation and regulates Wnt signaling. Neuron. 2011;71(1):103–16. Epub 2011/07/13. S0896-6273(11)00485-5 [pii] doi: 10.1016/j.neuron.2011.05.034 21745641; PubMed Central PMCID: PMC3134796.

74. Mercuri NB, Saiardi A, Bonci A, Picetti R, Calabresi P, Bernardi G, et al. Loss of autoreceptor function in dopaminergic neurons from dopamine D2 receptor deficient mice. Neuroscience. 1997;79(2):323–7. doi: 10.1016/s0306-4522(97)00135-8 9200717.

75. De Mei C, Ramos M, Iitaka C, Borrelli E. Getting specialized: presynaptic and postsynaptic dopamine D2 receptors. Curr Opin Pharmacol. 2009;9(1):53–8. doi: 10.1016/j.coph.2008.12.002 19138563; PubMed Central PMCID: PMC2710814.

76. Yim HJ, Gonzales RA. Ethanol-induced increases in dopamine extracellular concentration in rat nucleus accumbens are accounted for by increased release and not uptake inhibition. Alcohol. 2000;22(2):107–15. doi: 10.1016/s0741-8329(00)00121-x 11113625.

77. Imperato A, Di Chiara G. Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther. 1986;239(1):219–28. 3761194.

78. Weiss F, Parsons LH, Schulteis G, Hyytia P, Lorang MT, Bloom FE, et al. Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J Neurosci. 1996;16(10):3474–85. doi: 10.1523/JNEUROSCI.16-10-03474.1996 8627380.

79. Mitchell P, Mould R, Dillon J, Glautier S, Andrianakis I, James C, et al. A differential role for neuropeptides in acute and chronic adaptive responses to alcohol: behavioural and genetic analysis in Caenorhabditis elegans. PloS one. 2010;5(5):e10422. doi: 10.1371/journal.pone.0010422 20454655; PubMed Central PMCID: PMC2862703.

80. Topper SM, Aguilar SC, Topper VY, Elbel E, Pierce-Shimomura JT. Alcohol disinhibition of behaviors in C. elegans. PloS one. 2014;9(3):e92965. doi: 10.1371/journal.pone.0092965 24681782; PubMed Central PMCID: PMC3969370.

81. Benoit-Marand M, Jaber M, Gonon F. Release and elimination of dopamine in vivo in mice lacking the dopamine transporter: functional consequences. Eur J Neurosci. 2000;12(8):2985–92. doi: 10.1046/j.1460-9568.2000.00155.x 10971639.

82. Cass WA, Gerhardt GA. Direct in vivo evidence that D2 dopamine receptors can modulate dopamine uptake. Neurosci Lett. 1994;176(2):259–63. doi: 10.1016/0304-3940(94)90096-5 7830960.

83. Dickinson SD, Sabeti J, Larson GA, Giardina K, Rubinstein M, Kelly MA, et al. Dopamine D2 receptor-deficient mice exhibit decreased dopamine transporter function but no changes in dopamine release in dorsal striatum. J Neurochem. 1999;72(1):148–56. doi: 10.1046/j.1471-4159.1999.0720148.x 9886065.

84. Mayfield RD, Zahniser NR. Dopamine D2 receptor regulation of the dopamine transporter expressed in Xenopus laevis oocytes is voltage-independent. Mol Pharmacol. 2001;59(1):113–21. doi: 10.1124/mol.59.1.113 11125031.

85. Wu Q, Reith ME, Walker QD, Kuhn CM, Carroll FI, Garris PA. Concurrent autoreceptor-mediated control of dopamine release and uptake during neurotransmission: an in vivo voltammetric study. J Neurosci. 2002;22(14):6272–81. doi: 20026630 12122086.

86. Benoit-Marand M, Ballion B, Borrelli E, Boraud T, Gonon F. Inhibition of dopamine uptake by D2 antagonists: an in vivo study. J Neurochem. 2011;116(3):449–58. doi: 10.1111/j.1471-4159.2010.07125.x 21128941.

87. Bello EP, Mateo Y, Gelman DM, Noain D, Shin JH, Low MJ, et al. Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors. Nat Neurosci. 2011;14(8):1033–8. doi: 10.1038/nn.2862 21743470; PubMed Central PMCID: PMC3175737.

88. Anzalone A, Lizardi-Ortiz JE, Ramos M, De Mei C, Hopf FW, Iaccarino C, et al. Dual control of dopamine synthesis and release by presynaptic and postsynaptic dopamine D2 receptors. J Neurosci. 2012;32(26):9023–34. doi: 10.1523/JNEUROSCI.0918-12.2012 22745501; PubMed Central PMCID: PMC3752062.

89. Kennedy RT, Jones SR, Wightman RM. Dynamic observation of dopamine autoreceptor effects in rat striatal slices. J Neurochem. 1992;59(2):449–55. doi: 10.1111/j.1471-4159.1992.tb09391.x 1352798.

90. Beckstead MJ, Williams JT. Long-term depression of a dopamine IPSC. J Neurosci. 2007;27(8):2074–80. doi: 10.1523/JNEUROSCI.3251-06.2007 17314302.

91. Kong EC, Woo K, Li H, Lebestky T, Mayer N, Sniffen MR, et al. A pair of dopamine neurons target the D1-like dopamine receptor DopR in the central complex to promote ethanol-stimulated locomotion in Drosophila. PloS one. 2010;5(4):e9954. doi: 10.1371/journal.pone.0009954 20376353; PubMed Central PMCID: PMC2848596.

92. Abrahao KP, Quadros IM, Souza-Formigoni ML. Nucleus accumbens dopamine D(1) receptors regulate the expression of ethanol-induced behavioural sensitization. Int J Neuropsychopharmacol. 2011;14(2):175–85. doi: 10.1017/S1461145710000441 20426882.

93. Kass J, Jacob TC, Kim P, Kaplan JM. The EGL-3 proprotein convertase regulates mechanosensory responses of Caenorhabditis elegans. J Neurosci. 2001;21(23):9265–72. doi: 10.1523/JNEUROSCI.21-23-09265.2001 11717360.

94. Sieburth D, Madison JM, Kaplan JM. PKC-1 regulates secretion of neuropeptides. Nat Neurosci. 2007;10(1):49–57. doi: 10.1038/nn1810 17128266.

95. Jacob TC, Kaplan JM. The EGL-21 carboxypeptidase E facilitates acetylcholine release at Caenorhabditis elegans neuromuscular junctions. J Neurosci. 2003;23(6):2122–30. doi: 10.1523/JNEUROSCI.23-06-02122.2003 12657671.

96. Speese S, Petrie M, Schuske K, Ailion M, Ann K, Iwasaki K, et al. UNC-31 (CAPS) is required for dense-core vesicle but not synaptic vesicle exocytosis in Caenorhabditis elegans. J Neurosci. 2007;27(23):6150–62. doi: 10.1523/JNEUROSCI.1466-07.2007 17553987; PubMed Central PMCID: PMC6672138.

97. Bhardwaj A, Thapliyal S, Dahiya Y, Babu K. FLP-18 Functions through the G-Protein-Coupled Receptors NPR-1 and NPR-4 to Modulate Reversal Length in Caenorhabditis elegans. J Neurosci. 2018;38(20):4641–54. doi: 10.1523/JNEUROSCI.1955-17.2018 29712787.

98. Edwards SL, Charlie NK, Richmond JE, Hegermann J, Eimer S, Miller KG. Impaired dense core vesicle maturation in Caenorhabditis elegans mutants lacking Rab2. J Cell Biol. 2009;186(6):881–95. Epub 2009/10/03. jcb.200902095 [pii] doi: 10.1083/jcb.200902095 19797080; PubMed Central PMCID: PMC2753164.

99. Sumakovic M, Hegermann J, Luo L, Husson SJ, Schwarze K, Olendrowitz C, et al. UNC-108/RAB-2 and its effector RIC-19 are involved in dense core vesicle maturation in Caenorhabditis elegans. J Cell Biol. 2009;186(6):897–914. Epub 2009/10/03. jcb.200902096 [pii] doi: 10.1083/jcb.200902096 19797081; PubMed Central PMCID: PMC2753160.

100. Eddison M, Guarnieri DJ, Cheng L, Liu CH, Moffat KG, Davis G, et al. arouser reveals a role for synapse number in the regulation of ethanol sensitivity. Neuron. 2011;70(5):979–90. doi: 10.1016/j.neuron.2011.03.030 21658589.

101. Mitchell PH, Bull K, Glautier S, Hopper NA, Holden-Dye L, O'Connor V. The concentration-dependent effects of ethanol on Caenorhabditis elegans behaviour. Pharmacogenomics J. 2007;7(6):411–7. doi: 10.1038/sj.tpj.6500440 17325734.

102. Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974;77(1):71–94. 4366476.

103. Russell JSaD. Molecular Cloning: A Laboratory Manual. 2001.

104. Mello C, Fire A. DNA transformation. Methods Cell Biol. 1995;48:451–82. 8531738.

105. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676–82. doi: 10.1038/nmeth.2019 22743772; PubMed Central PMCID: PMC3855844.

106. Baidya M, Genovez M, Torres M, Chao MY. Dopamine modulation of avoidance behavior in Caenorhabditis elegans requires the NMDA receptor NMR-1. PloS one. 2014;9(8):e102958. doi: 10.1371/journal.pone.0102958 25089710; PubMed Central PMCID: PMC4121140.

107. Mahoney TR, Luo S, Nonet ML. Analysis of synaptic transmission in Caenorhabditis elegans using an aldicarb-sensitivity assay. Nat Protoc. 2006;1(4):1772–7. doi: 10.1038/nprot.2006.281 17487159.

108. Sieburth D, Ch'ng Q, Dybbs M, Tavazoie M, Kennedy S, Wang D, et al. Systematic analysis of genes required for synapse structure and function. Nature. 2005;436(7050):510–7. doi: 10.1038/nature03809 16049479.

109. Vashlishan AB, Madison JM, Dybbs M, Bai J, Sieburth D, Ch'ng Q, et al. An RNAi screen identifies genes that regulate GABA synapses. Neuron. 2008;58(3):346–61. Epub 2008/05/10. S0896-6273(08)00173-6 [pii] doi: 10.1016/j.neuron.2008.02.019 18466746.

110. Basu A, Dey S, Puri D, Das Saha N, Sabharwal V, Thyagarajan P, et al. let-7 miRNA controls CED-7 homotypic adhesion and EFF-1-mediated axonal self-fusion to restore touch sensation following injury. Proc Natl Acad Sci U S A. 2017;114(47):E10206–E15. doi: 10.1073/pnas.1704372114 29109254; PubMed Central PMCID: PMC5703274.

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