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



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.



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.



Our data indicate that the vSub → NAc shell glutamatergic projection, but not the vSub → vmPFC projection, contributes to context-induced reinstatement of heroin seeking.
Behavioral Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA. jbossert@intra.nida.nih.gov.
Jennifer M
JM
Bossert
Behavioral Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA.
Sweta
S
Adhikary
Behavioral Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA.
Robyn
R
St Laurent
Behavioral Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA.|Florey Institute of Neuroscience & Mental Health, University of Melbourne, Parkville, Australia.
Nathan J
NJ
Marchant
Integrative Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA.
Hui-Ling
HL
Wang
Integrative Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA.
Marisela
M
Morales
Behavioral Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA.
Yavin
Y
Shaham
D000818:Animals; D003463:Cues; D005108:Extinction, Psychological / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D003932:Heroin / Q000008:administration & dosage*; D006556:Heroin Dependence / Q000209:etiology / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration
D018698:Glutamic Acid; D003932:Heroin
Baclofen; Conditioned cues; Dopamine; Drug environment; Extinction; Fluoro-Gold; Fos; GABA; Glutamate; Heroin self-administration; Hippocampus; Muscimol; Opiates; Relapse; SCH 23390