Role of dopamine D1-like and D2-like receptors in the activation of ingestive behaviour in thirsty rats licking for water

  • Paolo S. D’AquilaEmail author
  • Domenico Elia
  • Adriana Galistu
Original Investigation



Analysis of lick pattern for sucrose and NaCl and of the forced swimming response after dopamine antagonist administration led us to suggest that dopamine on D1-like receptors is involved in behavioural activation, and the level of activation is “reboosted” on the basis of an evaluation process involving D2-like receptors. Although some studies investigated licking microstructure for water after dopamine antagonists, the within-session time course of their effect was never investigated.


The aims of this study were to further investigate the role of dopamine receptors in the mechanisms governing water ingestion, focussing on the within-session time course of the microstructure parameters, and to test the proposed hypothesis.

Materials and methods

The effects of the dopamine D1-like receptor antagonist SCH 23390 (0.01–0.04 mg/kg) and of the dopamine D2-like receptor antagonist raclopride (0.025–0.25 mg/kg) on licking microstructure for water were examined in 20-h water-deprived rats in 30-min sessions.


As previously observed with sucrose and NaCl, SCH 23390 reduced licking by reducing burst number, suggesting reduced behavioural activation. Moreover, it resulted in an increased burst size. Raclopride reduced the size of licking bursts, while their number was either increased or decreased depending on the dose.


The results support the suggestion that D1 receptors are involved in behavioural activation and D2 receptors are involved in a related evaluation process. Within the framework of the proposed hypothesis, the increased burst size after D1-like receptor blockade might be interpreted as a pro-hedonic effect consequent to the increased cost of the activation of the licking response.


Activation Dopamine Dopamine receptor Ingestion Motivation Reward 



The present study was funded by the Fondazione di Sardegna, Sassari, Italy.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Baird JP, St John SJ, Nguyen EA (2005) Temporal and qualitative dynamics of conditioned taste aversion processing: combined generalization testing and licking microstructure analysis. Behav Neurosci 119:983–1003CrossRefGoogle Scholar
  2. Berridge KC (2007) The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology 191:391–431CrossRefGoogle Scholar
  3. Berridge KC (2012) From prediction error to incentive salience: mesolimbic computation of reward motivation. Eur J Neurosci 35:1124–1143CrossRefGoogle Scholar
  4. Berridge KC, Venier IL, Robinson TE (1989) Taste reactivity analysis of 6-hydroxydopamine-induced aphagia: implications for arousal and anhedonia hypotheses of dopamine function. Behav Neurosci 103:36–45CrossRefGoogle Scholar
  5. Canon CM, Palmiter RD (2003) Reward without dopamine. J Neurosci 23:10827–10831CrossRefGoogle Scholar
  6. Canu ME, Carta D, Murgia E, Serra G, D’Aquila PS (2010) Dopamine on D2-like receptors is involved in reward evaluation in water-deprived rats licking for NaCl and water. Pharmacol Biochem Behav 96:194–197CrossRefGoogle Scholar
  7. Chausmer AL, Ettenberg A (1997) A role for D2, but not D1, dopamine receptors in the response-reinstating effects of food reinforcement. Pharmacol Biochem Behav 57:681–685CrossRefGoogle Scholar
  8. Clifton PG, Rusk IN, Cooper SJ (1991) Effects of dopamine D1 and dopamine D2 antagonists on the free feeding and drinking patterns of rats. Behav Neurosci 105:272–281CrossRefGoogle Scholar
  9. Cohen MX, Frank MJ (2009) Neurocomputational models of basal ganglia function in learning, memory and choice. Behav Brain Res 199:141–156CrossRefGoogle Scholar
  10. D’Aquila PS (2010) Dopamine on D2-like receptors “reboosts” dopamine D1-like receptor-mediated behavioural activation in rats licking for sucrose. Neuropharmacology 58:1085–1096CrossRefGoogle Scholar
  11. D’Aquila PS, Galistu A (2012) Possible role of dopamine D1-like and D2-like receptors in behavioural activation and evaluation of response efficacy in the forced swimming test. Neuropharmacology 62:1717–1729CrossRefGoogle Scholar
  12. D’Aquila PS, Galistu A (2017) Within-session decrement of the emission of licking bursts following reward devaluation in rats licking for sucrose. PLoS One 12(5):e0177705CrossRefGoogle Scholar
  13. D’Aquila PS, Rossi R, Rizzi A, Galistu A (2012) Possible role of dopamine D1-like and D2-like receptors in behavioural activation and “contingent” reward evaluation in sodium-replete and sodium-depleted rats licking for NaCl solutions. Pharmacol Biochem Behav 101:99–106CrossRefGoogle Scholar
  14. Davis JD (1989) The microstructure of ingestive behavior. Ann N Y Acad Sci 575:106–121CrossRefGoogle Scholar
  15. Davis JD, Smith GP (1992) Analysis of the microstructure of the rhythmic tongue movements of rats ingesting maltose and sucrose solutions. Behav Neurosci 106:217–228CrossRefGoogle Scholar
  16. Davis JD, Smith GP, Singh B (1999) A microstructural analysis of the control of water and isotonic saline ingestion by postingestional stimulation. Physiol Behav 66:543–548CrossRefGoogle Scholar
  17. De Santis M, Pan B, Lian J, Huang XF, Deng C (2014) Different effects of bifeprunox, aripiprazole, and haloperidol on body weight gain, food and water intake, and locomotor activity in rats. Pharmacol Biochem Behav 124:167–173CrossRefGoogle Scholar
  18. Didriksen M, Olsen GM, Christensen AV (1993) Effect of clozapine upon schedule-induced polydipsia (SIP) resembles neither the actions of dopamine D1 nor D2 blockade. Psychopharmacology 113:250–256CrossRefGoogle Scholar
  19. Dourish CT (1983) Dopaminergic involvement in the control of drinking behaviour: a brief review. Prog Neuro-Psychopharmacol Biol Psychiatry 7:487–493CrossRefGoogle Scholar
  20. Dourish DT, Jones RS (1982) Dopamine agonist-induced restoration of drinking in response to hypertonic saline in adipsic dopamine denervated rats. Brain Res Bull 8:375–379CrossRefGoogle Scholar
  21. Dwyer DM (2012) EPS Prize Lecture. Licking and liking: the assessment of hedonic responses in rodents. Q J Exp Psychol 65:371–394Google Scholar
  22. Ettenberg A, Camp CH (1986a) A partial reinforcement extinction effect in water-reinforced rats intermittently treated with haloperidol. Pharmacol Biochem Behav 1986 25:1231–1235CrossRefGoogle Scholar
  23. Ettenberg A, Camp CH (1986b) Haloperidol induces a partial reinforcement extinction effect in rats: implications for a dopamine involvement in food reward. Pharmacol Biochem Behav 25:813–821CrossRefGoogle Scholar
  24. Fortin SM, Roitman MF (2018) Challenges to body fluid homeostasis differentially recruit phasic dopamine signaling in a taste-selective manner. J Neurosci 38:6841–6853CrossRefGoogle Scholar
  25. Fowler SC, Mortell C (1992) Low doses of haloperidol interfere with rat tongue extensions during licking: a quantitative analysis. Behav Neurosci 106:386–395CrossRefGoogle Scholar
  26. Galistu A, D’Aquila PS (2012) Effect of the dopamine D1-like receptor antagonist SCH 23390 on the microstructure of ingestive behaviour in water-deprived rats licking for water and NaCl solutions. Physiol Behav 105:230–233CrossRefGoogle Scholar
  27. Galistu A, D’Aquila PS (2013) Dopamine on D2-like receptors “reboosts” dopamine D1-like receptor mediated behavioural activation in rats licking for a isotonic NaCl solution. Psychopharmacology 229:357–366CrossRefGoogle Scholar
  28. Galistu A, Modde C, Pireddu MC, Franconi F, Serra G, D’Aquila PS (2011) Clozapine increases reward evaluation but not overall ingestive behaviour in rats licking for sucrose. Psychopharmacology 216:411–420CrossRefGoogle Scholar
  29. Genn RF, Higgs S, Cooper SJ (2003) The effects of 7-OH-DPAT, quinpirole and raclopride on licking for sucrose solutions in the non-deprived rat. Behav Pharmacol 14:609–617CrossRefGoogle Scholar
  30. Gilbert DB, Cooper SJ (1987) Effects of the dopamine D-1 antagonist SCH 23390 and the D-2 antagonist sulpiride on saline acceptance-rejection in water-deprived rats. Pharmacol Biochem Behav 26:687–691CrossRefGoogle Scholar
  31. Gramling SE, Fowler SC (1986) Some effects of pimozide and of shifts in sucrose concentration on lick rate, duration, and interlick interval. Pharmacol Biochem Behav 25:219–222CrossRefGoogle Scholar
  32. Gramling SE, Fowler SC, Collins KR (1984) Some effects of pimozide on nondeprived rats licking sucrose solutions in an anhedonia paradigm. Pharmacol Biochem Behav 21:617–624CrossRefGoogle Scholar
  33. Haase HJ, Janssen PAJ (1985) The action of neuroleptic drugs. Elsevier, AmsterdamGoogle Scholar
  34. Higgs S, Cooper SJ (1998) Evidence for early opioid modulation of licking responses to sucrose and intralipid: a microstructural analysis in the rat. Psychopharmacology 139:342–355CrossRefGoogle Scholar
  35. Hsu TM, McCutcheon JE, Roitman MF (2018) Parallels and overlap: the integration of homeostatic signals by mesolimbic dopamine neurons. Front Psychiatry 9:410CrossRefGoogle Scholar
  36. Huang AC, Shyu BC, Hsiao S (2010) Dose-dependent dissociable effects of haloperidol on locomotion, appetitive responses, and consummatory behavior in water-deprived rats. Pharmacol Biochem Behav 95:285–291CrossRefGoogle Scholar
  37. Hurley SW, Arseth HA, Johnson AK (2018) Orexin neurons couple neural systems mediating fluid balance with motivation-related circuits. Behav Neurosci 132:284–292CrossRefGoogle Scholar
  38. Iorio LC, Barnett A, Leitz FH, Houser VP, Korduba CA (1983) SCH 23390, a potential benzazepine antipsychotic with unique interactions on dopaminergic systems. J Pharmacol Exp Ther 226:462–468Google Scholar
  39. Johnson AW (2018) Characterizing ingestive behavior through licking microstructure: underlying neurobiology and its use in the study of obesity in animal models. Int J Dev Neurosci 64:38–47CrossRefGoogle Scholar
  40. Johnson AW, Gallagher M (2011) Greater effort boosts the affective taste properties of food. Proc Biol Sci 278:1450–1456CrossRefGoogle Scholar
  41. Keitz M, Martin-Soelch C, Leenders KL (2003) Reward processing in the brain: a prerequisite for movement preparation? Neural Plast 10:121–128CrossRefGoogle Scholar
  42. Köhler C, Hall H, Ogren SO, Gawell L (1985) Specific in vitro and in vivo binding of 3H-raclopride. A potent substituted benzamide drug with high affinity for dopamine D-2 receptors in the rat brain. Biochem Pharmacol 34:2251–2259CrossRefGoogle Scholar
  43. Liao RM, Fowler SC (1990) Haloperidol produces within-session increments in operant response duration in rats. Pharmacol Biochem Behav 36:191–201CrossRefGoogle Scholar
  44. Liao RM, Ko MC (1995) Chronic effects of haloperidol and SCH23390 on operant and licking behaviors in the rat. Chin J Physiol 38:65–73Google Scholar
  45. Ljungberg T (1989a) Attenuation of water intake and operant responding by dopamine D2 antagonists: raclopride provides important cues for understanding the functional mechanism of action. Pharmacol Toxicol 65:9–12CrossRefGoogle Scholar
  46. Ljungberg T (1989b) Effects of the dopamine D-1 antagonist SCH 23390 on water intake, water-rewarded operant responding and apomorphine-induced decrease of water intake in rats. Pharmacol Biochem Behav 33:709–712CrossRefGoogle Scholar
  47. Ljungberg T (1990) Differential attenuation of water intake and water-rewarded operant responding by repeated administration of haloperidol and SCH 23390 in the rat. Pharmacol Biochem Behav 35:111–115CrossRefGoogle Scholar
  48. Lydall ES, Gilmour G, Dwyer DM (2010) Rats place greater value on rewards produced by high effort: an animal analogue of the “effort justification” effect. J Exp Soc Psychol 46:1134–1137CrossRefGoogle Scholar
  49. Marshall JF, Ungerstedt U (1976) Apomorphine-induced restoration of drinking to thirst challenges in 6-hydroxydopamine-treated rats. Physiol Behav 17:817–822CrossRefGoogle Scholar
  50. McFarland K, Ettenberg A (1995) Haloperidol differentially affects reinforcement and motivational processes in rats running an alley for intravenous heroin. Psychopharmacology 122:346–350CrossRefGoogle Scholar
  51. McFarland K, Ettenberg A (1998) Haloperidol does not affect motivational processes in an operant runway model of food seeking behavior. Behav Neurosci 112:630–635CrossRefGoogle Scholar
  52. Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998) Dopamine receptors: from structure to function. Physiol Rev 78:189–225CrossRefGoogle Scholar
  53. Pal GK, Bharathi B, Thombre DP (1992) Modulation of daily water intake by dopamine in caudate and accumbens nuclei in rats. Physiol Behav 51:851–856CrossRefGoogle Scholar
  54. Papp M, Bal A (1986) Motivational versus motor impairment after haloperidol injection or 6-OHDA lesions in the ventral tegmental area or substantia nigra in rats. Physiol Behav 38:773–779CrossRefGoogle Scholar
  55. Rick JH, Horvitz JC, Balsam PD (2006) Dopamine receptor blockade and extinction differentially affect behavioral variability. Behav Neurosci 120:488–492CrossRefGoogle Scholar
  56. Robbins TW, Everitt BJ (2007) A role for mesencephalic dopamine in activation: commentary on Berridge (2006). Psychopharmacology 191:433–437CrossRefGoogle Scholar
  57. Salamone JD (1986) Different effects of haloperidol and extinction on instrumental behaviours. Psychopharmacology 88:18–23CrossRefGoogle Scholar
  58. Salamone JD, Cousins MS, Snyder BJ (1997) Behavioral functions of nucleus accumbens dopamine: empirical and conceptual problems with the anhedonia hypothesis. Neurosci Biobehav Rev 21:341–359CrossRefGoogle Scholar
  59. Salamone JD, Correa M, Mingote SM, Weber SM (2005) Beyond the reward hypothesis: alternative functions of nucleus accumbens dopamine. Curr Opin Pharmacol 5:34–41Google Scholar
  60. Salamone JD, Correa M, Farrar A, Mingote SM (2007) Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology 191:461–482CrossRefGoogle Scholar
  61. Salamone JD, Correa M, Ferrigno S, Yang JH, Rotolo RA, Presby RE (2018) The psychopharmacology of effort-related decision making: dopamine, adenosine, and insights into the neurochemistry of motivation. Pharmacol Rev 70:747–762CrossRefGoogle Scholar
  62. Sanger DJ (1986) Response decrement patterns after neuroleptic and non-neuroleptic drugs. Psychopharmacology 89:98–104Google Scholar
  63. Schneider LH, Davis JD, Watson CA, Smith GP (1990) Similar effect of raclopride and reduced sucrose concentration on the microstructure of sucrose sham feeding. Eur J Pharmacol 186:61–70CrossRefGoogle Scholar
  64. Smith GP (2001) John Davis and the meanings of licking. Appetite 36:84–92CrossRefGoogle Scholar
  65. Smith GP, Smith JC (2010) The inhibitory potency of SCH 23390 and raclopride on licking for sucrose increases across brief-access tests. Physiol Behav 101:315–319CrossRefGoogle Scholar
  66. Spector AC, Klumpp PA, Kaplan JM (1998) Analytical issues in the evaluation of food deprivation and sucrose concentration effects on the microstructure of licking behavior in the rat. Behav Neurosci 112:678–694CrossRefGoogle Scholar
  67. Spivak KJ, Amit Z (1986) Effects of pimozide on appetitive behavior and locomotor activity: dissimilarity of effects when compared to extinction. Physiol Behav 36:457–463CrossRefGoogle Scholar
  68. Stricker EM (2012) Neurochemical and behavioral analyses of the lateral hypothalamic syndrome: a look back. Behav Brain Res 231:286–288CrossRefGoogle Scholar
  69. Tombaugh TN, Anisman H, Tombaugh J (1980) Extinction and dopamine receptor blockade after intermittent reinforcement training: failure to observe functional equivalence. Psychopharmacology 70:19–28CrossRefGoogle Scholar
  70. Tombaugh TN, Szostak C, Voorneveld P, Tombaugh JW (1982) Failure to obtain functional equivalence between dopamine receptor blockade and extinction: evidence supporting a sensory-motor conditioning hypothesis. Pharmacol Biochem Behav 16:67–72CrossRefGoogle Scholar
  71. Ukai M, Nakayama S, Kameyama T (1989) Inhibition of drinking by naltrexone in the rat: interaction with the dopamine D-1 antagonist SCH 23390 and the D-2 antagonist sulpiride. Pharmacol Biochem Behav 32:651–655CrossRefGoogle Scholar
  72. Ungerstedt U (1971) Adipsia and aphagia after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl 367:95–122CrossRefGoogle Scholar
  73. Wassum KM, Ostlund SB, Balleine BW, Maidment NT (2011) Differential dependence of Pavlovian incentive motivation and instrumental incentive learning processes on dopamine signaling. Learn Mem 18:475–483CrossRefGoogle Scholar
  74. Wise RA (1982a) Common neural basis for stimulation reward, drug reward and food reward. In: Hoebel BG, Novin D (eds) The neural basis of feeding and reward. Haer Institute for Electrophysiological Research, Brunswick, ME, pp 445–454Google Scholar
  75. Wise RA (1982b) Neuroleptics and operant behaviour: the anhedonia hypothesis. Behav Brain Sci 5:39–87CrossRefGoogle Scholar
  76. Wise RA (2004) Dopamine, learning and motivation. Nat Rev Neurosci 5:483–494CrossRefGoogle Scholar
  77. Wise RA (2006) Role of brain dopamine in food reward and reinforcement. Philos Trans R Soc Lond Ser B Biol Sci 361:1149–1158CrossRefGoogle Scholar
  78. Wise RA, Spindler J, deWit H, Gerberg GJ (1978) Neuroleptic-induced “anhedonia” in rats: pimozide blocks reward quality of food. Science 201:262–264CrossRefGoogle Scholar
  79. Zocchi D, Wennemuth G, Oka Y (2017) The cellular mechanism for water detection in the mammalian taste system. Nat Neurosci 20:927–933CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Dipartimento di Scienze BiomedicheUniversità di SassariSassariItaly

Personalised recommendations