Formation of a morphine-conditioned place preference does not change the size of evoked potentials in the ventral hippocampus\u2013nucleus accumbens projection

D Y Sakae,S J Martin

doi:10.1038/s41598-019-41568-5

Abstract

In opioid addiction, cues and contexts associated with drug reward can be powerful triggers for drug craving and relapse. The synapses linking ventral hippocampal outputs to medium spiny neurons of the accumbens may be key sites for the formation and storage of associations between place or context and reward, both drug-related and natural. To assess this, we implanted rats with electrodes in the accumbens shell to record synaptic potentials evoked by electrical stimulation of the ventral hippocampus, as well as continuous local-field-potential activity. Rats then underwent morphine-induced (10 mg/kg) conditioned-place-preference training, followed by extinction. Morphine caused an acute increase in the slope and amplitude of accumbens evoked responses, but no long-term changes were evident after conditioning or extinction of the place preference, suggesting that the formation of this type of memory does not lead to a net change in synaptic strength in the ventral hippocampal output to the accumbens. However, analysis of the local field potential revealed a marked sensitization of theta- and high-gamma-frequency activity with repeated morphine administration. This phenomenon may be linked to the behavioral changes—such as psychomotor sensitization and the development of drug craving—that are associated with chronic use of addictive drugs.

Highlights

The global health and social costs of opioid addiction are substantial and growing[1]
Histological analysis of post-mortem brain sections revealed that, in all rats used in the study, recording electrodes were located in the nucleus accumbens (NAcS) (Fig. 1E), and stimulating electrodes were located in ventral CA1 or subiculum (Fig. 1F)
Consistent with previous reports, we find that electrical stimulation of the ventral CA1/subiculum evokes a multi-component evoked field potential (EFP) in the nucleus accumbens shell, with a prominent positive peak at a latency of 10–12 ms

Summary

Introduction

The global health and social costs of opioid addiction are substantial and growing[1]. The VH provides a key link between hippocampal place information and the emotional, motivational, and executive systems of the brain[13,14,15] Consistent with this role, there is a prominent glutamatergic projection from area CA1 and the subiculum of the VH to the medium spiny neurons (MSNs) of the shell region of the nucleus accumbens (NAcS)[16,17,18,19]. The VH-NAcS pathway may convey spatial and contextual information to the NAc, which links this information to the presence or absence of reward[26] Consistent with its potential role in memory formation, the VH-NAc projection is plastic, exhibiting increases in synaptic strength in response to high-frequency electrical stimulation (e.g.23,28); these changes can be blocked by the application of an NMDA-receptor antagonist[28,29,30]. Synaptic changes have never been directly recorded in the NAc of intact, behaving animals during the formation of a context-reward association

Methods

Results

Conclusion