Non-Painful Peripheral Inflammation Blocks Conditioned Place-Preference to Morphine and Nicotine through an Ibuprofen-Sensitive and an Ibuprofen Insensitive Pathway

Marco Antonio Sotomayor-Sobrino,Eda Patricia Tenorio,Israel Luna-Mendoza,Claudia Gómez-Acevedo,Abraham Ochoa-Aguilar,Martha León-Olea,Roberto Velasco-González

doi:10.4236/jbbs.2018.82004

Abstract

The field of neuroimmunology has expanded in recent years providing new insights and therapies into pathologies like stroke, autism, and depression. However, few works explore the relationship between inflammatory stimuli and motivation. Thus, the aim of this study was to determine how non-painful inflammatory stimuli affect reward. To test reward-response, we used the morphine and the nicotine induced conditioned place-preference and place-aversion model in rats with non-painful inflammation. The following inflammatory models were used: non-painful infectious inflammation: 24 hrs prior to conditioning sessions, an injection with Calmette-Guerin bacillus (CGB) 1 × 107 cfu, ip, was administered. Non-painful non-infectious inflammation: 24 hrs prior to conditioning sessions, rats’ sciatic nerve was blocked and cut, followed by the injection of carrageenan (750 μl) in the paw. We then measured the cytokine concentration to determine the inflammatory profile of each of our models. Finally, we administered ibuprofen to determine if it could prevent the effect of inflammation over conditioned place-preference. We show that carrageenan significantly reduced the morphine-induced reward. Non-painful inflammatory stimulus, CGB and denervation + carrageenan, inhibit the conditioned place-preference to morphine and nicotine, CGB also block conditioned place-aversion to nicotine; carrageenan has no effect on CPA. The administration of ibuprofen reinstates conditioned place-preference to morphine and nicotine in the carrageenan model, but has no effect in the CGB model; finally ibuprofen has no effect on CPA. Our data suggest that non-painful-inflammatory stimuli inhibit the reward system, independent of cytokine concentration. Furthermore, the administration of a PGE 2 inhibitor can importantly modulate this phenomenon.

Highlights

The brain motivation system is an intricate set of interconnected structures with powerful effects on behavior, eliciting a range of conducts from normal and necessary to pathological
Our results show that non-painful inflammation induced with a high concentration of carrageenan blocks conditioned place-preference (CPP)
Our results support previous findings indicating that painful-inflammation can decrease CPP induced by morphine [18]

Summary

Introduction

The brain motivation system is an intricate set of interconnected structures with powerful effects on behavior, eliciting a range of conducts from normal and necessary to pathological The influence of this system is relevant within the context of substance addiction [1]. Studies in animal models have shown that repeated exposure to a drug promotes robust self-administration, conditioned place-preference and consumption preference [1], while in humans, it generates compulsive use and dependence [2]. These effects are the culprit of the current drug-use epidemics such as tobacco and opioids consumption in the world [2] [3]. Morphine administration has been reported to activate dopaminergic neurons indirectly through an interneuron pathway [7] and the administration of dopamine antagonists in the NAc has shown to diminish the opioid self-administration response [8]; the role of dopamine in opioid reward and addiction is inconsistent and, it is often not considered as the key mechanism [9]

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