, Volume 219, Issue 1, pp 159–169 | Cite as

Roles of D1-like dopamine receptors in the nucleus accumbens and dorsolateral striatum in conditioned avoidance responses

  • Evellyn Claudia Wietzikoski
  • Suelen Lúcio Boschen
  • Edmar Miyoshi
  • Mariza Bortolanza
  • Lucélia Mendes dos Santos
  • Michael Frank
  • Marcus Lira Brandão
  • Philip Winn
  • Claudio Da Cunha
Original Investigation



Aversively motivated learning is more poorly understood than appetitively motivated learning in many aspects, including the role of dopamine receptors in different regions of the striatum.


The present study investigated the roles of the D1-like DA receptors in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) on learning and performance of conditioned avoidance responses (CARs).


Adult male Wistar rats received intraperitoneal (i.p.), intra-NAc, or intra-DLS injections of the D1 dopamine receptor agonist SKF 81297 or the D1 receptor antagonist SCH 23390 20 min before or immediately after a training session in the CAR task two-way active avoidance, carried out 24 h before a test session.


Pre-training administration of SCH 23390, but not SKF 81297, caused a significant decrease in the number of CARs in the test, but not in the training session, when injected into the DLS, or in either session when injected into the NAc. It also caused a significant increase in the number of escape failures in the training session when injected into the NAc. Systemic administration caused a combination of these effects. Post-training administrations of these drugs caused no significant effect.


The results suggest that the D1-like receptors in the NAc and DLS play important, though different, roles in learning and performance of CAR.


Dorsolateral striatum Nucleus accumbens D1 dopamine receptor Two-way active avoidance Conditioned avoidance learning Memory Decision-making 


  1. Aguilar MA, Mari-Sanmillan MI, Morant-Deusa JJ, Minarro J (2000) Different inhibition of conditioned avoidance response by clozapine and DA D-1 and D-2 antagonists in male mice. Behav Neurosci 114:389–400PubMedCrossRefGoogle Scholar
  2. Alexander GE, Crutcher MD, Delong MR (1990) Basal ganglia–thalamocortical circuits — parallel substrates for motor, oculomotor, prefrontal and limbic functions. Prog Brain Res 85:119–146PubMedCrossRefGoogle Scholar
  3. Balleine BW, O’Doherty JP (2010) Human and rodent homologies in action control: corticostriatal determinants of goal-directed and habitual action. Neuropsychopharmacology 35:48–69PubMedCrossRefGoogle Scholar
  4. Beninger RJ, Rolfe NG (1995) Dopamine D1-like receptor agonists impair responding for conditioned reward in rats. Behav Pharmacol 6:785–793PubMedCrossRefGoogle Scholar
  5. Beninger RJ, Mason ST, Phillips AG, Fibiger HC (1980) The use of conditioned suppression to evaluate the nature of neuroleptic-induced avoidance deficits. J Pharmacol Exp Ther 213:623–627PubMedGoogle Scholar
  6. Berridge KC (2007) The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology 131:391–431CrossRefGoogle Scholar
  7. Brischoux F, Chakraborty S, Brierley DI, Ungless MA (2009) Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli. Proc Natl Acad Sci U S A 106:4893–4899CrossRefGoogle Scholar
  8. Carlezon WA, Thomas MJ (2009) Biological substrates of reward and aversion: a nucleus accumbens activity hypothesis. Neuropharmacology 56:122–132PubMedCrossRefGoogle Scholar
  9. Da Cunha C, Gevaerd MS, Vital M, Miyoshi E, Andreatini R, Silveira R, Takahashi RN, Canteras NS (2001) Memory disruption in rats with nigral lesions induced by MPTP: a model for early Parkinson’s disease amnesia. Behav Brain Res 124:9–18PubMedCrossRefGoogle Scholar
  10. Da Cunha C, Wietzikoski EC, Dombrowski P, Santos LM, Bortolanza M, Boschen SL, Miyoshi E (2009) Learning processing in the basal ganglia: a mosaic of broken mirrors. Behav Brain Res 199:156–169Google Scholar
  11. Di Chiara G (2002) Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav Brain Res 137:75–114PubMedCrossRefGoogle Scholar
  12. Ferreira JGP, Del-Fava F, Hasue RH, Shammah-Lagnado SJ (2008) Organization of ventral tegmental area projections to the ventral tegmental area–nigral complex in the rat. Neuroscience 153:196–213PubMedCrossRefGoogle Scholar
  13. Floresco SB, Phillips AG (1999) Dopamine and hippocampal input to the nucleus accumbens play an essential role in the search for food in an unpredictable environment. Psychobiology 27:277–286Google Scholar
  14. Frank MJ, Seeberger LC, O’Reilly RC (2004) By carrot or by stick: cognitive reinforcement learning in parkinsonism. Science 306:1940–1943PubMedCrossRefGoogle Scholar
  15. Gal G, Schiller D, Weiner I (2005) Latent inhibition is disrupted by nucleus accumbens shell lesion but is abnormally persistent following entire nucleus accumbens lesion: the neural site controlling the expression and disruption of the stimulus preexposure effect. Behav Brain Res 162:246–255PubMedCrossRefGoogle Scholar
  16. Gevaerd MS, Miyoshi E, Silveira R, Canteras NS, Takahashi RN, Da Cunha C (2001a) l-dopa restores striatal dopamine level but fails to reverse MPTP-induced memory deficits in rats. Int J Neuropsychopharmacol 4:361–370PubMedCrossRefGoogle Scholar
  17. Gevaerd MS, Takahashi RN, Silveira R, Da Cunha C (2001b) Caffeine reverses the memory disruption induced by intra-nigral MPTP-injection in rats. Brain Res Bull 55:101–106PubMedCrossRefGoogle Scholar
  18. Goto Y, Grace AA (2008) Limbic and cortical information processing in the nucleus accumbens. Trends Neurosci 31:552–558PubMedCrossRefGoogle Scholar
  19. Hernandez-Lopez S, Bargas J, Surmeier DJ, Reyes A, Galarraga E (1987) D1 receptor activation enhances evoked discharge in neostriatal medium spiny neurons by modulating an l-type Ca2+ conductance. J Neurosci Methods 17:3334–3342Google Scholar
  20. Hikida T, Kimura K, Wada N, Funabiki K, Nakanishi S (2010) Distinct roles of synaptic transmission in direct and indirect striatal pathways to reward and aversive behavior. Neuron 66:896–907PubMedCrossRefGoogle Scholar
  21. Horvitz JC (2000) Mesolimbocortical and nigrostriatal dopamine responses to salient non-reward events. Neuroscience 96:651–656PubMedCrossRefGoogle Scholar
  22. Iorio LC, Cohen M, Coffin VL (1991) Anticholinergic drugs potentiate dopamine D1 but not D2 antagonists on a conditioned avoidance task in rats. J Pharmacol Exp Ther 258:118–123PubMedGoogle Scholar
  23. Izquierdo LA, Barros DM, da Costa JC, Furini C, Zinn C, Carnmarota M, Bevilaqua LR, Izquierdo I (2007) A link between role of two prefrontal areas in immediate memory and in long-term memory consolidation. Neurobiol Learn Mem 88:160–166PubMedCrossRefGoogle Scholar
  24. LaLumiere RT, Nguyen LT, McGaugh JL (2004) Post-training intrabasolateral amygdala infusions of dopamine modulate consolidation of inhibitory avoidance memory: involvement of noradrenergic and cholinergic systems. Eur J Neurosci 20:2804–2810PubMedCrossRefGoogle Scholar
  25. Lapointe NP, Guertin PA (2008) Synergistic effects of D-1/5 and 5-HT1a/7 receptor agonists on locomotor movement induction in complete spinal cord-transected mice. J Neurophysiol 100:160–168PubMedCrossRefGoogle Scholar
  26. Lorens SA, Sorensen JP, Harvey JA (1970) Lesions in nuclei accumbens septi of rat — behavioral and neurochemical effects. J Comp Physiol Psychol 73:284PubMedCrossRefGoogle Scholar
  27. Lovinger DM (2010) Neurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum. Neuropharmacology 58:951–961PubMedCrossRefGoogle Scholar
  28. Maia TV (2010) Two-factor theory, the actor–critic model, and conditioned avoidance. Learn Behav 38:50–67PubMedCrossRefGoogle Scholar
  29. Matamales M, Bertran-Gonzalez J, Salomon L, Degos B, Deniau JM, Valjent E, Herve D, Girault JA (2009) Striatal medium-sized spiny neurons: identification by nuclear staining and study of neuronal subpopulations in bac transgenic mice. PLoS One 4:e4770PubMedCrossRefGoogle Scholar
  30. Matsumoto M, Hikosaka O (2009) Two types of dopamine neuron distinctly convey positive and negative motivational signals. Nature 459:838–842CrossRefGoogle Scholar
  31. McGaugh JL, Roozendaal B (2009) Drug enhancement of memory consolidation: historical perspective and neurobiological implications. Psychopharmacology 202:3–14PubMedCrossRefGoogle Scholar
  32. McGeorge AJ, Faull RLM (1989) The organization of the projection from the cerebral cortex to the striatum in the rat. Neuroscience 29:503–537PubMedCrossRefGoogle Scholar
  33. Morris G, Schmidt R, Bergman H (2010) Striatal action-learning based on dopamine concentration. Exp Brain Res 200:307–317PubMedCrossRefGoogle Scholar
  34. Moutoussis M, Bentall RP, Williams J, Dayan P (2008) A temporal difference account of avoidance learning. Netw Comput Neural Syst 19:137–160CrossRefGoogle Scholar
  35. Nauta WJH, Smith GP, Faull RLM, Domesick VB (1978) Efferent connections and nigral afferents of nucleus accumbens septi in rat. Neuroscience 3:385–401PubMedCrossRefGoogle Scholar
  36. Nicola SM (2007) The nucleus accumbens as part of a basal ganglia action selection circuit. Psychopharmacology 191:521–550PubMedCrossRefGoogle Scholar
  37. Nicola SM, Surmeier DT, Malenka RC (2000) Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. Annu Rev Neurosci 23:185–215PubMedCrossRefGoogle Scholar
  38. Ogren SO, Archer T (1994) Effects of typical and atypical antipsychotic-drugs on 2-way active-avoidance — relationship to DA receptor blocking profile. Psychopharmacology 114:383–391PubMedCrossRefGoogle Scholar
  39. Oliveira AR, Reimer AE, Brandao ML (2009) Role of dopamine receptors in the ventral tegmental area in conditioned fear. Behav Brain Res 199:271–277PubMedCrossRefGoogle Scholar
  40. Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates. Academic Press, San Diego, EUAGoogle Scholar
  41. Ragozzino ME, Ragozzino KE, Mizumori SJY, Kesner RP (2002) Role of the dorsomedial striatum in behavioral flexibility for response and visual cue discrimination learning. Behav Neurosci 116:105–115PubMedCrossRefGoogle Scholar
  42. Redgrave P, Gurney K, Reynolds J (2008) What is reinforced by phasic dopamine signals? Brain Res Rev 58:322–339PubMedCrossRefGoogle Scholar
  43. Reis FLV, Masson S, de Oliveira AR, Brandao ML (2004) Dopaminergic mechanisms in the conditioned and unconditioned fear as assessed by the two-way avoidance and light switch-off tests. Pharmacol Biochem Behav 79:359–365PubMedCrossRefGoogle Scholar
  44. Rossato JI, Bevilaqua LRM, Izquierdo I, Medina JH, Cammarota M (2009) Dopamine controls persistence of long-term memory storage. Science 325:1017–1020PubMedCrossRefGoogle Scholar
  45. Schmidt HD, Pierce RC (2006) Cooperative activation of D1-like and D2-like dopamine receptors in the nucleus accumbens shell is required for the reinstatement of cocaine-seeking behavior in the rat. Neuroscience 142:451–461PubMedCrossRefGoogle Scholar
  46. Schultz W (2010) Dopamine signals for reward value and risk: basic and recent data. Behav Brain Funct 6:9CrossRefGoogle Scholar
  47. Sesack SR, Grace AA (2010) Cortico-basal ganglia reward network: microcircuitry. Neuropsychopharmacology 35:27–47PubMedCrossRefGoogle Scholar
  48. Shen WX, Flajolet M, Greengard P, Surmeier DJ (2008) Dichotomous dopaminergic control of striatal synaptic plasticity. Science 321:848–851PubMedCrossRefGoogle Scholar
  49. Stuchlik A, Vales K (2006) Effect of dopamine D1 receptor antagonist SCH23390 and D1 agonist a77636 on active allothetic place avoidance, a spatial cognition task. Behav Brain Res 172:250–255PubMedCrossRefGoogle Scholar
  50. Surmeier DJ, Ding J, Day M, Wang ZF, Shen WX (2007) D1 and D2 dopamine-receptor modulation of striatal glutamatergic signalling in striatal medium spiny neurons. Trends Neurosci 30:228–235PubMedCrossRefGoogle Scholar
  51. Torras-Garcia M, Costa-Miserachs D, Morgado-Bernal I, Portell-Cortes I (2003) Improvement of shuttle-box performance by anterodorsal medial septal lesions in rats. Behav Brain Res 141:147–158PubMedCrossRefGoogle Scholar
  52. Voorn P, Vanderschuren L, Groenewegen HJ, Robbins TW, Pennartz CMA (2004) Putting a spin on the dorsal–ventral divide of the striatum. Trends Neurosci 27:468–474PubMedCrossRefGoogle Scholar
  53. Wadenberg ML (1992) Antagonism by 8-OH-DPAT, but not ritanserin, of catalepsy induced by SCH-23390 in the rat. J Neural Transm Gen Sect 89:49–59PubMedCrossRefGoogle Scholar
  54. West AR, Grace AA (2002) Opposite influences of endogenous dopamine D-1 and D-2 receptor activation on activity states and electrophysiological properties of striatal neurons: studies combining in vivo intracellular recordings and reverse microdialysis. J Neurosci 22:294–304PubMedGoogle Scholar
  55. Wickens JR, Horvitz JC, Costa RM, Killcross S (2007) Dopaminergic mechanisms in actions and habits. J Neurosci 27:8181–8183PubMedCrossRefGoogle Scholar
  56. Wiecki TV, Frank MJ (2010) Neurocomputational models of motor and cognitive deficits in Parkinson’s disease. Recent advances in Parkinson’s disease: basic research. Prog Brain Res 183:275–297PubMedCrossRefGoogle Scholar
  57. Williams GV, Castner SA (2006) Under the curve: critical issues for elucidating D1 receptor function in working memory. Neuroscience 139:263–276PubMedCrossRefGoogle Scholar
  58. Wise RA (2008) Dopamine and reward: the anhedonia hypothesis 30 years on. Neurotox Res 14:69–83CrossRefGoogle Scholar
  59. Woodruff ML, Fish BS, Alderman AO (1977) Epileptiform lesions in rat hippocampus and acquisition of 2-way avoidance. Physiol Behav 19:401–410PubMedCrossRefGoogle Scholar
  60. Yin HH, Knowlton BJ (2006) The role of the basal ganglia in habit formation. Nat Rev Neurosci 7:464–476PubMedCrossRefGoogle Scholar
  61. Yin HH, Knowlton BJ, Balleine BW (2006) Inactivation of dorsolateral striatum enhances sensitivity to changes in the action-outcome contingency in instrumental conditioning. Behav Brain Res 166:189–196PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Evellyn Claudia Wietzikoski
    • 1
  • Suelen Lúcio Boschen
    • 1
  • Edmar Miyoshi
    • 1
    • 2
  • Mariza Bortolanza
    • 1
  • Lucélia Mendes dos Santos
    • 1
  • Michael Frank
    • 3
  • Marcus Lira Brandão
    • 4
  • Philip Winn
    • 5
  • Claudio Da Cunha
    • 1
  1. 1.Departamento de FarmacologiaLaboratório de Fisiologia e Farmacologia do Sistema Nervoso CentraCuritibaBrazil
  2. 2.Departamento de Ciências FarmacêuticasUEPGPonta GrossaBrazil
  3. 3.Department of Cognitive, Linguistic and Psychological Sciences, Department of Psychiatry and Human Behavior, Brown Institute for Brain ScienceBrown UniversityProvidenceUSA
  4. 4.Instituto de Neurociencias e Comportamento – IneCRibeirão PretoBrazil
  5. 5.Strathclyde Institute of Pharmacy and Biomedical SciencesUniversity of StrathclydeGlasgowUK

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