dCA1-NAc shell glutamatergic projection mediates context-induced memory recall of morphine

Abstract

Opioid relapse is generally caused by the recurrence of context-induced memory reinstatement of reward. However, the internal mechanisms that facilitate and modify these processes remain unknown. One of the key regions of the reward is the nucleus accumbens (NAc) which receives glutamatergic projections from the dorsal hippocampus CA1 (dCA1). It is not yet known whether the dCA1 projection to the NAc shell regulates the context-induced memory recall of morphine. Here, we used a common model of addiction-related behavior conditioned place preference paradigm, combined with immunofluorescence, chemogenetics, optogenetics, and electrophysiology techniques to characterize the projection of the dCA1 to the NAc shell, in context-induced relapse memory to morphine. We found that glutamatergic neurons of the dCA1 and gamma aminobutyric acidergic (GABA) neurons of the NAc shell are the key brain areas and neurons involved in the context-induced reinstatement of morphine memory. The dCA1-NAc shell glutamatergic input pathway and the excitatory synaptic transmission of the dCA1-NAc shell were enhanced via the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) when mice were re-exposed to environmental cues previously associated with drug intake. Furthermore, chemogenetic and optogenetic inactivation of the dCA1-NAc shell pathway decreased the recurrence of long- and short-term morphine-paired context memory in mice. These results provided evidence that the dCA1-NAc shell glutamatergic projections mediated the context-induced memory recall of morphine.

Keywords: AMPA (PubChem CID: 1221); CNO (PubChem CID:135445691); CNQX (PubChem CID: 6093155); Conditioned place preference; Dorsal hippocampus; GABA (PubChem CID: 119); Glutamatergic projection; Glutamic acid (PubChem CID: 611); KCl (PubChem CID: 4873); MK 801 (PubChem CID: 180081); Morphine; Morphine (PubChem CID: 528886); NMDA (PubChem CID: 22880); NaCl (PubChem CID: 5234); Nucleus accumbens; Relapse memory.