Skip to main content
Log in

Reciprocal responsiveness of nucleus accumbens shell and core dopamine to food- and drug-conditioned stimuli

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Drugs of abuse and palatable food share the ability to stimulate dopamine (DA) transmission in the nucleus accumbens shell. However, while the stimulation of shell DA by food undergoes habituation, that by drugs of abuse does not.

Objective

This study aims to directly compare the changes of extracellular DA, by microdialysis, in shell and core and prefrontal cortex (PFCX) in response to food- and drug-conditioned stimuli (CSs).

Methods

Rats were trace-conditioned by Fonzies box (FB) or vanilla box (VB; CS), followed by food: Fonzies, intraoral chocolate solution (food-unconditioned stimulus (US)) and morphine (1.0 mg/Kg sc; drug US). Control (unconditioned) rats received standard food instead of Fonzies, tap water instead of chocolate, saline instead of morphine.

Results

Food–CSs increased core but not shell DA, while drug–CSs did the opposite. Food and drug–CSs both increased PFCX DA. Exposure to food–CSs potentiated core and PFCX DA response to food while shell responsiveness was dependent upon the relative CS and US nature. If the CS was intrinsic to the food US (CS = FB/US = Fonzies) the response of shell DA to the US was abolished. If the CS was extrinsic to the food US (CS = FB/US = chocolate; CS = VB/US = Fonzies), shell DA increased in response to the US. Exposure to the drug–CS potentiated the DA response to the drug–US in the shell and in the PFCX, but not in the core.

Conclusion

Drug–CSs differentially activate DA as compared to food–CSs in shell and core and differentially affect DA response to the US in these areas. These differences might be relevant for the role of DA in the mechanism of drug addiction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Aragona BJ, Cleaveland NA, Stuber GD, Day JJ, Carelli RM, Wightman RM (2008) Preferential enhancement of dopamine transmission within the nucleus accumbens shell by cocaine is attributable to a direct increase in phasic dopamine release events. J Neurosci 28(35):8821–8831

    Article  PubMed  CAS  Google Scholar 

  • Aragona BJ, Day JJ, Roitman MF, Cleaveland NA, Wightman RM, Carelli RM (2009) Regional specificity in the real-time development of phasic dopamine transmission patterns during acquisition of a cue–cocaine association in rats. E J Neurosci 30:1889–1899

    Article  Google Scholar 

  • Avena MN, Rada P, Hoebel BG (2008) Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev 32(1):20–39

    Article  PubMed  CAS  Google Scholar 

  • Bassareo V, Di Chiara G (1997) Differential influence of associative and nonassociative learning mechanisms on the responsiveness of prefrontal and accumbal dopamine transmission to food stimuli in rats fed ad libitum. J Neurosci 17(2):851–861

    PubMed  CAS  Google Scholar 

  • Bassareo V, Di Chiara G (1999a) Differential responsiveness of DA transmission to food stimuli in nucleus accumbens shell/core compartments. Neurosci 89(3):637–641

    Article  CAS  Google Scholar 

  • Bassareo V, Di Chiara G (1999b) Modulation of feeding-induced activation of mesolimbic dopamine transmission by appetitive stimuli and its relation to motivational state. Eur J Neurosci 11:4389–4397

    Article  PubMed  CAS  Google Scholar 

  • Bassareo V, De Luca MA, Aresu M, Aste A, Ariu T, Di Chiara G (2003) Differential adaptive properties of accumbens shell dopamine response to ethanol as a drug and as a motivational stimulus. Eur J Neurosci 17(7):1465–1472

    Article  PubMed  Google Scholar 

  • Bassareo V, De Luca MA, Di Chiara G (2007) Differential impact of pavlovian drug conditioned stimuli on in vivo dopamine transmission in the rat accumbens shell and core and in the prefrontal cortex. Psychopharmacology 191:689–703

    Article  PubMed  CAS  Google Scholar 

  • Bassareo V, Musio P, Lecca D, Di Chiara G (2009) Mesolimbic dopamine responsiveness to food conditioned stimuli after instrumental conditioning paradigm. Behav Pharmacol 20(special issue):S37, Abstracts of the 13th Biennal EBPS meeting

    Google Scholar 

  • Blackburn JR, Pfaus JG, Phillips AG (1992) Dopamine functions in appetitive and defensive behaviours. Prog Neurobiol 39(3):247–279

    Article  PubMed  CAS  Google Scholar 

  • Cacciapaglia F, Owesson-White CA, Wheeler RA, Wightman RM, Carelli RM (2008) Nucleus accumbens cell firing and rapid dopamine release during food-seeking behavior in rats. Society for Neuroscience Abstract, Washington DC

    Google Scholar 

  • Cadoni C, Di Chiara G (1999) Reciprocal changes in dopamine responsiveness in the nucleus accumbens shell and core and in the dorsal caudate-putamen in rats sensitized to morphine. Neurosci 90(2):447–455

    Article  CAS  Google Scholar 

  • Cheng JJ, de Bruin JPC, Feenstra MGP (2003) Dopamine efflux in nucleus accumbens shell and core in response to appetitive classical conditioning. E J Neurosci 18:1306–1314

    Article  CAS  Google Scholar 

  • Ciccocioppo R, Martin-Fardon R, Weiss F (2002) Effect of selective blockade of μ1 and δ opioid receptors on reinstatement of alcohol-seeking behavior by drug-associated stimuli in rats. Neuropsychopharmacology 27(3):391–399

    Article  PubMed  CAS  Google Scholar 

  • Danielli B, Scheggi S, Grappi S, Marchese G, De Montis MG, Tagliamonte A, Gambarana C (2009) Modifications in DARPP-32 phosphorylation pattern after repeated palatable food consumption undergo rapid habituation in the nucleus accumbens shell of non food-deprived rats. J Neurochem 112(2):531–541

    Article  PubMed  Google Scholar 

  • Di Chiara G (1998) A motivational learning hypothesis of the role of mesolimbic dopamine in compulsive drug use. J Psychopharmacol 12(1):54–67

    Article  PubMed  Google Scholar 

  • Di Chiara G (2002) Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav Brain Res 137:75–114

    Article  PubMed  Google Scholar 

  • Di Chiara G (2005) Dopamine in disturbance of food and drug motivated behavior: a case of homology? Physiol Behav 86:9–10

    Article  PubMed  Google Scholar 

  • Di Chiara G, Bassareo V (2007) Reward system and addiction: what dopamine does and doesn’t do. Curr Opin Pharmacol 7:69–76

    Article  PubMed  Google Scholar 

  • Di Chiara G, Tanda G, Frau R, Carboni E (1993) On the preferential release of dopamine in the nucleus accumbens by amphetamine: further evidence obtained by vertically implanted concentric dialysis probes. Psychopharmacol 112:98–402

    Google Scholar 

  • Di Chiara G, Bassareo V, Fenu S, De Luca MA, Spina L, Cadoni C, Acquas E, Carboni E, Valentini V, Lecca D (2004) Dopamine and drug addiction: the nucleus accumbens shell connection. Neuropharmacology 47(Suppl 1):227–241

    PubMed  Google Scholar 

  • Everitt BJ, Parkinson JA, Olmstead MC, Arroyo M, Robledo P, Robbins TW (1999) Associative processes in addiction and reward. The role of amygdala–ventral striatal subsystems. Ann n Y Acad Sci 877:412–438

    Article  PubMed  CAS  Google Scholar 

  • Fenu S, Spina L, Rivas E, Di Chiara G (2006) Morphine-conditioned single-trial place preference: role of nucleus accumbens shell dopamine receptors in acquisition, but not expression. Psychopharmacol Berl 187:143–153

    Article  CAS  Google Scholar 

  • Fuchs RA, Bell GH, Ramirez DR, Eaddy JL, Su ZI (2009) Basolateral amygdala involvement in memory reconsolidation processes that facilitate drugcontext-induced cocaine seeking. Eur J Neurosi 30:889–900

    Article  Google Scholar 

  • Gambarana C, Masi M, Leggio B, Grappi S, Nanni G, Scheggi S, De Montis MG, Tagliamonte A (2003) Acquisition of a palatable food-sustained appetitive behavior in satiated rats is dependent on the dopaminergic response to this food in limbic areas. Neuroscience 121:179–187

    Article  PubMed  CAS  Google Scholar 

  • Hajnal A, Smith GP, Norgren R (2004) Oral sucrose stimulation increases accumbens dopamine in the rat. Am J Physiol Regul Integr Comp Physiol 286:R31–R37

    PubMed  CAS  Google Scholar 

  • Ito R, Dalley JW, Howes SR, Robbins TW, Everitt BJ (2000) Dissociation in conditioned dopamine release in the nucleus accumbens core and shell in response to cocaine cues and during cocaine-seeking behavior in rats. J Neurosci 20:7489–7495

    PubMed  CAS  Google Scholar 

  • Liang NC, Hajnal A, Norgren R (2006) Sham feeding corn oil increases accumbens dopamine in the rat. Am J Physiol Regul Integr Comp Physiol 291:R1236–R1239

    PubMed  CAS  Google Scholar 

  • Parkinson JA, Olmstead MC, Burns LH, Robbins TW, Everitt BJ (1999) Dissociation in effects of lesions of nucleus accumbens core and shell in appetitive Pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by d-amphetamine. J Neurosci 19:2401–2411

    PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates IV ed Academic Press New York

  • Phillips PE, Stuber GD, Heien ML, Wightman RM, Carelli RM (2003) Subsecond dopamine release promotes cocaine seeking. Nature 422(6932):614–618

    Article  PubMed  CAS  Google Scholar 

  • Pontieri FE, Tanda G, Di Chiara G (1995) Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the “shell” as compared with the “core” of the rat nucleus accumbens. Proc Natl Acad Sci USA 92:12304–12308

    Article  PubMed  CAS  Google Scholar 

  • Pontieri FE, Tanda G, Orzi F, Di Chiara G (1996) Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 382:255–257

    Article  PubMed  CAS  Google Scholar 

  • Rada P, Avena NM, Hoebel BG (2005) Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell. Neuroscience 134:737–744

    Article  PubMed  CAS  Google Scholar 

  • Ramirez DR, Bell GH, Lasseter HC, Xie X, Traina SA, Fuchs RA (2009) Dorsal hippocampal regulation of memory reconsolidationprocesses that facilitate drug context-induced cocaine-seeking behavior in rats. Eur J Neurosci 30:901–912

    Article  PubMed  Google Scholar 

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive–sensitization theory of addiction. Brain Res Rev 18:247–291

    Article  PubMed  CAS  Google Scholar 

  • Roitman MR, Phillips PEM, Stuber G, Wightman RM, Carelli RM (2004) Dopamine operates as a subsecond modulator of food seeking. J Neurosci 24(6):1265–1271

    Article  PubMed  CAS  Google Scholar 

  • Sclafani A, Ackroff K (1994) Glucose- and fructose-conditioned flavor preferences in rats: taste versus post-ingestive conditioning. Physiol Behav 56:399–405

    Article  PubMed  CAS  Google Scholar 

  • Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacol Berl 168(1-2):3–20

    Article  CAS  Google Scholar 

  • Spina L, Fenu S, Rivas E, Di Chiara G (2006) Nicotine-conditioned single-trial place preference: selective role of nucleus accumbens shell dopamine D1 receptors in acquisition. Psychopharmacol Berl 84:447–455

    Article  Google Scholar 

  • Stewart J, de Wit H, Eikelboom R (1984) Role of unconditioned and conditioned drug affects in the self-administration of opiates and stimulants. Psychol Rev 91:251–268

    Article  PubMed  CAS  Google Scholar 

  • Tanda G, Bassareo V, Di Chiara G (1996) Mianserin markedly and selectively increases extracellular dopamine in the prefrontal cortex as compared to the nucleus accumbens of the rat. Psychopharmacol 123:127–130

    Article  CAS  Google Scholar 

  • Tanda G, Pontieri FE, Di Chiara G (1997) Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Science 276:2048–2050

    Article  PubMed  CAS  Google Scholar 

  • Volkow ND, Wang GJ, Ma Y, Fowler JS, Zhu W, Maynard L, Telang F, Vaska P, Ding YS, Wong C, Swanson JM (2003) Expectation enhances the regional brain metabolic and reinforcing effects of stimulants in cocaine abusers. J Neurosci 23(36):11461–11468

    PubMed  CAS  Google Scholar 

  • Woodruff-Pak DS, Disterhoft JF (2008) Where is the trace in trace conditioning? Trends Neurosci 31(2):105–112

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gaetano Di Chiara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bassareo, V., Musio, P. & Di Chiara, G. Reciprocal responsiveness of nucleus accumbens shell and core dopamine to food- and drug-conditioned stimuli. Psychopharmacology 214, 687–697 (2011). https://doi.org/10.1007/s00213-010-2072-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-010-2072-8

Keywords

Navigation