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Role of projections from ventral subiculum to nucleus accumbens shell in context-induced reinstatement of heroin seeking in rats

Abstract

Rationale and objective

In humans, exposure to contexts previously associated with heroin use can provoke relapse. In rats, exposure to heroin-paired contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. We previously demonstrated that the projections from ventral medial prefrontal cortex (vmPFC) to nucleus accumbens (NAc) shell play a role in this reinstatement. The ventral subiculum (vSub) sends glutamate projections to NAc shell and vmPFC. Here, we determined whether these projections contribute to context-induced reinstatement.

Methods

We trained rats to self-administer heroin (0.05–0.1 mg/kg/infusion) for 3 h per day for 12 days; drug infusions were paired with a discrete tone–light cue. Lever pressing in the presence of the discrete cue was subsequently extinguished in a different context. We then tested the rats for reinstatement in the heroin- and extinction-associated contexts under extinction conditions. We combined Fos with the retrograde tracer Fluoro-Gold (FG) to determine projection-specific activation during the context-induced reinstatement tests. We also used anatomical disconnection procedures to determine whether the vSub → NAc shell and vSub → vmPFC projections are functionally involved in this reinstatement.

Results

Exposure to the heroin but not the extinction context reinstated lever pressing. Context-induced reinstatement of heroin seeking was associated with increased Fos expression in vSub neurons, including those projecting to NAc shell and vmPFC. Anatomical disconnection of the vSub → NAc shell projection, but not the vSub → vmPFC projection, decreased this reinstatement.

Conclusions

Our data indicate that the vSub → NAc shell glutamatergic projection, but not the vSub → vmPFC projection, contributes to context-induced reinstatement of heroin seeking.

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Acknowledgments

This research was supported by the National Institute on Drug Abuse, Intramural Research Program. This paper is part of a special issue entitled “Addiction research and the legacy of Steven R. Goldberg” and is dedicated to Dr. Steven Goldberg, a valued friend, colleague, and a pioneer in addiction research.

Conflict of interest

The authors declare that they do not have any conflicts of interest (financial or otherwise) related to the data presented in this manuscript.

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Correspondence to Jennifer M. Bossert.

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Bossert, J.M., Adhikary, S., St. Laurent, R. et al. Role of projections from ventral subiculum to nucleus accumbens shell in context-induced reinstatement of heroin seeking in rats. Psychopharmacology 233, 1991–2004 (2016). https://doi.org/10.1007/s00213-015-4060-5

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Keywords

  • Baclofen
  • Conditioned cues
  • Dopamine
  • Drug environment
  • Extinction
  • Fluoro-Gold
  • Fos
  • GABA
  • Glutamate
  • Heroin self-administration
  • Hippocampus
  • Muscimol
  • Opiates
  • Relapse
  • SCH 23390