Psychopharmacology

, Volume 197, Issue 3, pp 449–456 | Cite as

The rewarding effect of aggression is reduced by nucleus accumbens dopamine receptor antagonism in mice

Original Investigation

Abstract

Rationale

Dopamine (DA) receptors within the nucleus accumbens (NAc) are implicated in the rewarding properties of stimuli. Aggressive behavior can be reinforcing but the involvement of NAc DA in the reinforcing effects of aggression has yet to be demonstrated.

Objective

To microinject DA receptor antagonists into the NAc to dissociate their effects on reinforcement from their effects on aggressive behavior and general movement.

Materials and methods

Male Swiss Webster mice were implanted with guide cannulae aimed for the NAc and tested for aggressive behavior in a resident–intruder procedure. Aggressive mice were then conditioned on a variable-ratio 5 (VR-5) schedule with presentation of the intruder as the reinforcing event. The D1- and D2-like receptor antagonists SCH-23390 and sulpiride were microinfused (12–50 ng) before the mice responded on the VR-5 schedule and attacked the intruder. Open-field activity was also determined following the highest doses of these drugs.

Results

SCH-23390 and sulpiride dose-dependently reduced VR responding but did not affect open-field activity. The 50-ng SCH-23390 dose suppressed response rates by 40% and biting behaviors by 10%; other aggressive behaviors were not affected. The 25 and 50 ng sulpiride doses almost completely inhibited VR responding; the 50-ng dose suppressed biting by 50%.

Conclusions

These results suggest that both D1- and D2-like receptors in the ventral striatum are involved in the rewarding properties of aggression, but that D1-like receptors may be related to the motivation to earn reinforcement as opposed to aggressive behavior.

Keywords

Aggression Dopamine Nucleus accumbens Reward Operant behavior Positive reinforcement Resident–intruder Mice 

Notes

Acknowledgements

This work was supported by a Discovery Grant (CHK) from Vanderbilt University. We thank Jon Tapp for his computer programming and Andrea Gaede and Michael May for their laboratory assistance.

References

  1. Baggio G, Ferrari F (1980) Role of brain dopaminergic mechanisms in rodent aggressive behavior: influence of (±, −)N-n-propylnorapomorphine on three experimental models. Psychopharmacology (Berl) 70:63–68CrossRefGoogle Scholar
  2. Berridge KC (2007) The debate over dopamine's role in reward: the case for incentive salience. Psychopharmacology (Berl) 191:391–431CrossRefGoogle Scholar
  3. Bourne JA (2001) SCH 23390: the first selective dopamine D1-like receptor antagonist. CNS Drug Rev 7:399–414PubMedCrossRefGoogle Scholar
  4. Chaplin EH (2006) Forensic aspects in people with intellectual disabilities. Curr Opin Psychiatry 19:486–491PubMedCrossRefGoogle Scholar
  5. Cherek D, Thompson T, Heistad GT (1973) Responding maintained by the opportunity to attach during an interval food reinforcement schedule. J Exp Anal Behav 19:113–123PubMedCrossRefGoogle Scholar
  6. Corrigall WA, Franklin KB, Coen KM, Clarke PB (1992) The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine. Psychopharmacology (Berl) 107:285–289CrossRefGoogle Scholar
  7. De Almeida RMM, Miczek KA (2002) Aggression escalated by social instigation or by discontinuation of reinforcement (“frustration”) in mice. Neuropsychopharmacology 27:171–181PubMedCrossRefGoogle Scholar
  8. De Almeida RM, Rosa MM, Santos DM, Saft DM, Benini Q, Miczek KA (2006) 5-HT(1B) receptors, ventral orbitofrontal cortex, and aggressive behavior in mice. Psychopharmacology (Berl) 185:441–450CrossRefGoogle Scholar
  9. de Boer SF, Koolhaas JM (2005) 5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis. Eur J Pharmacol 526:125–139PubMedCrossRefGoogle Scholar
  10. de Wit H, Wise RA (1977) Blockade of cocaine reinforcement in rats with the dopamine receptor blocker pimozide, but not with the noradrenergic blockers phentolamine or phenoxybenzamine. Can J Psychol 31:195–203PubMedGoogle Scholar
  11. Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A 85:5274–5278PubMedCrossRefGoogle Scholar
  12. Drago J, Padungchaichot P, Accili D, Fuchs S (1998) Dopamine receptors and dopamine transporter in brain function and addictive behaviors: insights from targeted mouse mutants. Dev Neurosci 20:188–203PubMedCrossRefGoogle Scholar
  13. Ferrari PF, Van Erp AAM, Tornatzky W, Miczek KA (2003) Accumbal dopamine and serotonin in anticipation of the next aggressive episode in rats. Eur J Neurosci 17:371–378PubMedCrossRefGoogle Scholar
  14. Fish EW, De Bold JF, Miczek KA (2002) Aggressive behavior as a reinforcer in mice: activation by allopregnanolone. Psychopharmacology (Berl) 163:459–466CrossRefGoogle Scholar
  15. Fish EW, DeBold JF, Miczek KA (2005) Escalated aggression as a reward: corticosterone and GABA(A) receptor positive modulators in mice. Psychopharmacology (Berl) 182:116–127CrossRefGoogle Scholar
  16. Floresco SB, Ghods-Sharifi S, Vexelman C, Magyar O (2006) Dissociable roles for the nucleus accumbens core and shell in regulating set shifting. J Neurosci 26:2449–2257PubMedCrossRefGoogle Scholar
  17. Hara Y, Pickel VM (2005) Overlapping intracellular and differential synaptic distributions of dopamine D1 and glutamate N-methyl-d-aspartate receptors in rat nucleus accumbens. J Comp Neurol 492:442–55PubMedCrossRefGoogle Scholar
  18. Kudryavtseva NN, Lipina TV, Koryakina LA (1999) Effects of haloperidol on communicative and aggressive behavior in male mice with different experiences of aggression. Pharmacol Biochem Behav 63:229–236PubMedCrossRefGoogle Scholar
  19. Laraway S, Snycerski S, Michael J, Poling A (2003) Motivating operations and terms to describe them: some further refinements. J Appl Behav Anal 36:407–414PubMedCrossRefGoogle Scholar
  20. McFarland K, Ettenberg A (1995) Haloperidol differentially affects reinforcement and motivational processes in rats running an alley for intravenous heroin. Psychopharmacology (Berl) 122:346–350CrossRefGoogle Scholar
  21. Michael J (1982) Distinguishing between discriminative and motivational functions of stimuli. J Exp Anal Behav 37:149–155PubMedCrossRefGoogle Scholar
  22. Miczek KA, Fish EW, De Bold JF, De Almeida RM (2002) Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and gamma-aminobutyric acid systems. Psychopharmacology (Berl) 163:434–548CrossRefGoogle Scholar
  23. Miczek KA, Maxson SC, Fish EW, Faccidomo S (2001) Aggressive behavioral phenotypes in mice. Behav Brain Res 125:167–181PubMedCrossRefGoogle Scholar
  24. Miczek KA, O, 'Donnell JM (1978) Intruder-evoked aggression in isolated and nonisolated mice: effects of psychomotor stimulants and l-DOPA. Psychopharmacology (Berl) 57:47–55CrossRefGoogle Scholar
  25. Nelson J (2006) Biology of aggression. Oxford University, New YorkGoogle Scholar
  26. Nestler EJ (2004) Molecular mechanisms of drug addiction. Neuropharmacology 47(Suppl 1):24–32PubMedCrossRefGoogle Scholar
  27. Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates. Academic, New YorkGoogle Scholar
  28. Pezze MA, Dalley JW, Robbins TW (2007) Differential roles of dopamine D1 and D2 receptors in the nucleus accumbens in attentional performance on the five-choice serial reaction time task. Neuropsychopharmacology 32:273–283PubMedCrossRefGoogle Scholar
  29. Rodriguez-Arias M, Minarro J, Aguilar MA, Pinazo J, Simon VM (1998) Effects of risperidone and SCH 23390 on isolationinduced aggression in male mice. Eur Neuropsychopharmacol 8:95–103PubMedCrossRefGoogle Scholar
  30. Scott JP (1958) Aggression. University of Chicago, ChicagoGoogle Scholar
  31. Sellings LH, Clarke PB (2003) Segregation of amphetamine reward and locomotor stimulation between nucleus accumbens medial shell and core. J Neurosci 23:6295–6303PubMedGoogle Scholar
  32. Sellings LH, Clarke PB (2006) 6-Hydroxydopamine lesions of nucleus accumbens core abolish amphetamine-induced conditioned activity. Synapse 59:374–377PubMedCrossRefGoogle Scholar
  33. Shram MJ, Funk D, Li Z, Le AD (2007) Acute nicotine enhances c-fos mRNA expression differentially in reward-related substrates of adolescent and adult rat brain. Neurosci Lett 418:286–291PubMedCrossRefGoogle Scholar
  34. Siegel A, Roeling TAP, Gregg T, Kruk MR (1999) Neuropharmacology of brain-stimulation-evoked aggression. Neurosci Biobehav Rev 23:359–389PubMedCrossRefGoogle Scholar
  35. Sokolov BP, Cadet JL (2006) Methamphetamine causes alterations in the MAP kinase-related pathways in the brains of mice that display increased aggressiveness. Neuropsychopharmacology 31:956–966PubMedCrossRefGoogle Scholar
  36. Steiner H, Saxena K, Chang K (2003) Psychopharmacologic strategies for the treatment of aggression in juveniles. CNS Spectr 8:298–308PubMedGoogle Scholar
  37. Thompson T (1963) Visual reinforcement in Siamese fighting fish. Science 141:55–57PubMedCrossRefGoogle Scholar
  38. van Erp AM, Miczek KA (2000) Aggressive behavior, increased accumbal dopamine, and decreased cortical serotonin in rats. J Neurosci 20:9320–9325PubMedGoogle Scholar
  39. van Erp AM, Miczek KA (2007) Increased accumbal dopamine during daily alcohol consumption and subsequent aggressive behavior in rats. Psychopharmacology (Berl) 191:679–688CrossRefGoogle Scholar
  40. Wise RA (2004) Dopamine, learning, and motivation. Nat Rev Neurosci 5:483–495PubMedCrossRefGoogle Scholar
  41. Wise RA, Spindler J, deWit H, Gerberg GJ (1978) Neuroleptic-induced “anhedonia” in rats: pimozide blocks reward quality of food. Science 201:262–264PubMedCrossRefGoogle Scholar
  42. Yokel RA, Wise RA (1975) Increased lever pressing for amphetamine after pimozide in rats: implications for a dopamine theory of reward. Science 187:547–549PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Vanderbilt Kennedy CenterVanderbilt UniversityNashvilleUSA
  2. 2.Center for Integrative and Cognitive NeuroscienceVanderbilt UniversityNashvilleUSA
  3. 3.Department of Special EducationVanderbilt UniversityNashvilleUSA
  4. 4.Department of PediatricsVanderbilt University Medical CenterNashvilleUSA

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