Morphine self-administration decreases intrinsic excitability of accumbal medium spiny neurons and suppresses the innate immune system in male Wistar rats

Abstract

Introduction

Morphine alleviates severe pain but is addictive and associated with weakened immune system. Interestingly, the immunosuppressive effects have been linked to central circuits including the nucleus accumbens shell (NAc), suggesting that there might be a direct link between reward processing in the NAc and weakened immune system. The overall aim with this study was to assess the impact displayed by morphine self-administration on neuroplasticity in the NAc shell and circulating white blood cells.

Methods

Wistar rats received morphine injections over ten days, and locomotor activity was monitored. Next, morphine self-administration, and relapse drinking after forced abstinence, were assessed. Lastly, electrophysiological recordings were conducted in the NAc ex vivo to define neurophysiological adaptations, and hematological analysis were conducted in parallel.

Results

While ten days of morphine injections were not sufficient to affect morphine self-administration, behavioral sensitization to the locomotor stimulatory properties of morphine was observed and further correlated with the amount of morphine consumed following forced abstinence. Electrophysiological slice recordings demonstrated no effect on excitatory neurotransmission, but the intrinsic excitability of NAc neurons was significantly depressed compared to water drinking controls. In addition, hematological analysis demonstrated a significant decline in the number of white blood cells, especially monocytes and neutrophils, while erythrocytes were not affected. The amount of circulating white blood cells further correlated with morphine intake, but not with neurophysiological parameters.

Conclusion

The data presented here demonstrates that morphine self-administration produces accumbal neuroplasticity and biological transformations that could contribute to the addictive and immunosuppressive properties of morphine.