Jennifer M Bossert1, Sweta Adhikary2, Robyn St Laurent2, Nathan J Marchant2,3, Hui-Ling Wang4, Marisela Morales4, Yavin Shaham2. 1. Behavioral Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA. jbossert@intra.nida.nih.gov. 2. Behavioral Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA. 3. Florey Institute of Neuroscience & Mental Health, University of Melbourne, Parkville, Australia. 4. Integrative Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA.
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.
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.
Authors: Christina L Lebonville; Jacqueline E Paniccia; Shveta V Parekh; Lynde M Wangler; Meghan E Jones; Rita A Fuchs; Donald T Lysle Journal: Brain Behav Immun Date: 2020-07-24 Impact factor: 7.217
Authors: John Strang; Nora D Volkow; Louisa Degenhardt; Matthew Hickman; Kimberly Johnson; George F Koob; Brandon D L Marshall; Mark Tyndall; Sharon L Walsh Journal: Nat Rev Dis Primers Date: 2020-01-09 Impact factor: 52.329
Authors: Jacqueline E Paniccia; Christina L Lebonville; Meghan E Jones; Shveta V Parekh; Rita A Fuchs; Donald T Lysle Journal: Brain Behav Immun Date: 2018-07-31 Impact factor: 7.217
Authors: David J Reiner; Ida Fredriksson; Olivia M Lofaro; Jennifer M Bossert; Yavin Shaham Journal: Neuropsychopharmacology Date: 2018-10-06 Impact factor: 7.853