Advertisement

Psychopharmacology

, Volume 194, Issue 3, pp 321–331 | Cite as

The role of dorsal vs ventral striatal pathways in cocaine-seeking behavior after prolonged abstinence in rats

  • R. E. See
  • J. C. Elliott
  • M. W. Feltenstein
Original Investigation

Abstract

Rationale

Recent studies have implicated an important role for the dorsal striatum during craving for cocaine and in cocaine-seeking after abstinence in rats.

Objectives

We compared the effects of pharmacological inactivation of mesencephalic dopamine (DA) cell body regions and dorsal vs ventral striatal terminal fields in an animal model of relapse after chronic cocaine self-administration.

Materials and methods

Rats self-administered cocaine for 2 h/day for ten sessions, followed by 2 weeks of abstinence (i.e., no extinction training). Immediately before being returned to the self-administration chamber, we assessed the effects of gamma-aminobutyric acid agonist inhibition of midbrain DA regions (substantia nigra [SN] and ventral tegmental area [VTA]) and striatum (dorsolateral caudate–putamen, nucleus accumbens core, and nucleus accumbens shell) on relapse to cocaine-seeking in the absence of reinforcement. Further testing examined daily extinction responding subsequent to the initial relapse test.

Results

Inactivation of the dorsal caudate–putamen and midbrain regions attenuated cocaine seeking, while inactivation of the ventral striatum had no such effects. However, subsequent sessions under extinction conditions revealed a rebound in cocaine seeking in animals that had undergone inactivation in all regions except the dorsolateral caudate–putamen.

Conclusions

The dorsal but not ventral striatum plays a critical role in cocaine seeking immediately after abstinence. These data support the theory that chronic cocaine may shift activity from the ventral to dorsal striatum during drug seeking under certain conditions. While not necessary at the time of relapse, the ventral striatum appears to be involved in processing critical information of the relapse event.

Keywords

Cocaine Extinction Reinstatement Relapse Self-administration Striatum 

Notes

Acknowledgments

We thank Ritu Mehta and Alisha Henderson for providing excellent technical assistance. This research was supported by National Institute on Drug Abuse grants DA10462 and DA15369 and NIH grant C06 RR015455.

References

  1. Berridge KC, Robinson TE (1998) What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience. Brain Res Brain Res Rev 28:309–369PubMedCrossRefGoogle Scholar
  2. Canales JJ (2005) Stimulant-induced adaptations in neostriatal matrix and striosome systems: transiting from instrumental responding to habitual behavior in drug addiction. Neurobiol Learn Mem 83:93–103PubMedCrossRefGoogle Scholar
  3. Curran EJ, Akil H, Watson SJ (1996) Psychomotor stimulant- and opiate-induced c-fos mRNA expression patterns in the rat forebrain: comparisons between acute drug treatment and a drug challenge in sensitized animals. Neurochem Res 21:1425–1435PubMedCrossRefGoogle Scholar
  4. Dackis CA, O’Brien CP (2001) Cocaine dependence: a disease of the brain’s reward centers. J Subst Abuse Treat 21:111–117PubMedCrossRefGoogle Scholar
  5. Epstein DH, Preston KL (2003) The reinstatement model and relapse prevention: a clinical perspective. Psychopharmacology 168:31–41PubMedCrossRefGoogle Scholar
  6. Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8:1481–1489PubMedCrossRefGoogle Scholar
  7. Fallon JH, Moore RY (1978) Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum. J Comp Neurol 180:545–580PubMedCrossRefGoogle Scholar
  8. Ferreira TL, Moreira KM, Ikeda DC, Bueno OF, Oliveira MG (2003) Effects of dorsal striatum lesions in tone fear conditioning and contextual fear conditioning. Brain Res 987:17–24PubMedCrossRefGoogle Scholar
  9. Fuchs RA, See RE (2002) Basolateral amygdala inactivation abolishes conditioned stimulus- and heroin-induced reinstatement of extinguished heroin-seeking behavior in rats. Psychopharmacology 160:425–433PubMedCrossRefGoogle Scholar
  10. Fuchs RA, Evans KA, Parker MC, See RE (2004a) Differential involvement of the core and shell subregions of the nucleus accumbens in conditioned cue-induced reinstatement of cocaine seeking in rats. Psychopharmacology 176:459–465CrossRefGoogle Scholar
  11. Fuchs RA, Evans KA, Parker MP, See RE (2004b) Differential involvement of orbitofrontal cortex subregions in conditioned cue-induced and cocaine-primed reinstatement of cocaine seeking in rats. J Neurosci 24:6600–6610CrossRefGoogle Scholar
  12. Fuchs RA, Branham RK, See RE (2006a) Different neural substrates mediate cocaine seeking after abstinence versus extinction training: a critical role for the dorsolateral caudate–putamen. J Neurosci 26:3584–3588CrossRefGoogle Scholar
  13. Fuchs RA, Feltenstein MW, See RE (2006b) The role of the basolateral amygdala in stimulus–reward memory and extinction memory consolidation and in subsequent conditioned-cued reinstatement of cocaine seeking. Eur J Neurosci 23:2809–2813CrossRefGoogle Scholar
  14. Gerdeman GL, Partridge JG, Lupica CR, Lovinger DM (2003) It could be habit forming: drugs of abuse and striatal synaptic plasticity. Trends Neurosci 26:184–192PubMedCrossRefGoogle Scholar
  15. Ghitza UE, Fabbricatore AT, Prokopenko V, Pawlak AP, West MO (2003) Persistent cue-evoked activity of accumbens neurons after prolonged abstinence from self-administered cocaine. J Neurosci 23:7239–7245PubMedGoogle Scholar
  16. Graybiel AM, Moratalla R, Robertson HA (1990) Amphetamine and cocaine induce drug-specific activation of the c-fos gene in striosome-matrix compartments and limbic subdivisions of the striatum. Proc Natl Acad Sci USA 87:6912–6916PubMedCrossRefGoogle Scholar
  17. Haber SN, Kim KS, Mailly P, Calzavara R (2006) Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning. J Neurosci 26:8368–8376PubMedCrossRefGoogle Scholar
  18. Hollander JA, Carelli RM (2005) Abstinence from cocaine self-administration heightens neural encoding of goal-directed behaviors in the accumbens. Neuropsychopharmacology 30:1464–1474PubMedCrossRefGoogle Scholar
  19. 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 20:7489–7495PubMedGoogle Scholar
  20. Ito R, Dalley JW, Robbins TW, Everitt BJ (2002) Dopamine release in the dorsal striatum during cocaine-seeking behavior under the control of a drug-associated cue. J Neurosci 22:6247–6253PubMedGoogle Scholar
  21. Letchworth SR, Nader MA, Smith HR, Friedman DP, Porrino LJ (2001) Progression of changes in dopamine transporter binding site density as a result of cocaine self-administration in rhesus monkeys. J Neurosci 21:2799–2807PubMedGoogle Scholar
  22. Marinelli M, Cooper DC, Baker LK, White FJ (2003) Impulse activity of midbrain dopamine neurons modulates drug-seeking behavior. Psychopharmacology 168:84–98PubMedCrossRefGoogle Scholar
  23. McFarland K, Kalivas PW (2001) The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 21:8655–8663PubMedGoogle Scholar
  24. McFarland K, Davidge SB, Lapish CC, Kalivas PW (2004) Limbic and motor circuitry underlying footshock-induced reinstatement of cocaine-seeking behavior. J Neurosci 24:1551–1560PubMedCrossRefGoogle Scholar
  25. McLaughlin J, See RE (2003) Selective inactivation of the dorsomedial prefrontal cortex and the basolateral amygdala attenuates conditioned-cued reinstatement of extinguished cocaine-seeking behavior in rats. Psychopharmacology 168:57–65PubMedCrossRefGoogle Scholar
  26. Nader MA, Daunais JB, Moore T, Nader SH, Moore RJ, Smith HR, Friedman DP, Porrino LJ (2002) Effects of cocaine self-administration on striatal dopamine systems in rhesus monkeys: initial and chronic exposure. Neuropsychopharmacology 27:35–46PubMedCrossRefGoogle Scholar
  27. O’Brien CP, Childress AR, Ehrman R, Robbins SJ (1998) Conditioning factors in drug abuse: can they explain compulsion. J Psychopharmacol 12:15–22PubMedCrossRefGoogle Scholar
  28. Paxinos G, Watson D (1986) The rat brain in stereotaxic coordinates. Academic, New YorkGoogle Scholar
  29. Pickens R, Thompson T (1968) Cocaine-reinforced behavior in rats: effects of reinforcement magnitude and fixed-ratio size. J Pharmacol Exp Ther 161:122–129PubMedGoogle Scholar
  30. Porrino LJ, Daunais JB, Smith HR, Nader MA (2004a) The expanding effects of cocaine: studies in a nonhuman primate model of cocaine self-administration. Neurosci Biobehav Rev 27:813–820CrossRefGoogle Scholar
  31. Porrino LJ, Lyons D, Smith HR, Daunais JB, Nader MA (2004b) Cocaine self-administration produces a progressive involvement of limbic, association, and sensorimotor striatal domains. J Neurosci 24:3554–3562CrossRefGoogle Scholar
  32. Robbins SJ, Ehrman RN (1998) Cocaine use is associated with increased craving in outpatient cocaine abusers. Exp Clin Psychopharmacol 6:217–224PubMedCrossRefGoogle Scholar
  33. Schuster CR, Johanson CE (1981) An analysis of drug-seeking behavior in animals. Neurosci Biobehav Rev 5:315–323PubMedCrossRefGoogle Scholar
  34. See RE (2005) Neural substrates of cocaine-cue associations that trigger relapse. Eur J Pharmacol 526:140–146PubMedCrossRefGoogle Scholar
  35. Self DW, Genova LM, Hope BT, Barnhart WJ, Spencer JJ, Nestler EJ (1998) Involvement of cAMP-dependent protein kinase in the nucleus accumbens in cocaine self-administration and relapse of cocaine-seeking behavior. J Neurosci 18:1848–1859PubMedGoogle Scholar
  36. Self DW, Choi KH, Simmons D, Walker JR, Smagula CS (2004) Extinction training regulates neuroadaptive responses to withdrawal from chronic cocaine self-administration. Learn Mem 11:648–657PubMedCrossRefGoogle Scholar
  37. Shaham Y, Shalev U, Lu L, Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology 168:3–20PubMedCrossRefGoogle Scholar
  38. Shalev U, Highfield D, Yap J, Shaham Y (2000) Stress and relapse to drug seeking in rats: studies on the generality of the effect. Psychopharmacology 150:337–346PubMedCrossRefGoogle Scholar
  39. Stewart J (2000) Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking. J Psychiatry Neurosci 25:125–136PubMedGoogle Scholar
  40. Sutton MA, Schmidt EF, Choi KH, Schad CA, Whisler K, Simmons D, Karanian DA, Monteggia LM, Neve RL, Self DW (2003) Extinction-induced upregulation in AMPA receptors reduces cocaine-seeking behaviour. Nature 421:70–75PubMedCrossRefGoogle Scholar
  41. Vanderschuren LJ, Ciano P, Everitt BJ (2005) Involvement of the dorsal striatum in cue-controlled cocaine seeking. J Neurosci 25:8665–8670PubMedCrossRefGoogle Scholar
  42. Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Hitzemann R, Chen AD, Dewey SL, Pappas N (1997) Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature 386:830–833PubMedCrossRefGoogle Scholar
  43. Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Childress AR, Jayne M, Ma Y, Wong C (2006) Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction. J Neurosci 26:6583–6588PubMedCrossRefGoogle Scholar
  44. Wong DF, Kuwabara H, Schretlen DJ, Bonson KR, Zhou Y, Nandi A, Brasic JR, Kimes AS, Maris MA, Kumar A, Contoreggi C, Links J, Ernst M, Rousset O, Zukin S, Grace AA, Lee JS, Rohde C, Jasinski DR, Gjedde A, London ED (2006) Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving. Neuropsychopharmacology 31:2716–2727PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • R. E. See
    • 1
  • J. C. Elliott
    • 1
  • M. W. Feltenstein
    • 1
  1. 1.Department of NeurosciencesMedical University of South CarolinaCharlestonUSA

Personalised recommendations