A Dual Investigation of Questions in Drug Addiction: Exploring the Role of Neuroinflammation in Opioid Withdrawal and A Novel Measure of Reward-Seeking Behavior in Rodents

Abstract

Substance abuse disorders are extremely disruptive to the lives and relationships of those who suffer from them and are a burden on society and the healthcare system. Effective treatments are currently lacking and our understanding of the neurobiology driving addictive behaviors remains incomplete. The following animal studies aimed to advance the drug addiction field by 1) investigating neuroimmune interactions as a potential mechanism in opioid withdrawal in mice as well as 2) introducing a novel behavioral test in order to expand the repertoire of tools available to researchers investigating drug or reward-seeking behaviors in rats. Microglia, the immune cells of the brain have been recently recognized as being important contributors in a wide variety of neuropsychiatric disorders, including drug addiction. Although current views support a microglia role in the physical drug dependence experienced by opioids addicts, it is thought that the emotional effects of withdrawal, such as anxiety and depression, are better predictors of relapse. In the first series of experiment, a genetic mouse model lacking the key microglia immune receptor TLR4 was used to determine the involvement of this protein in the molecular and behavioral responses to opioid withdrawal, in particular those related to negative emotions. Although technological advances in behavioral testing techniques have improved our ability to model drug addiction in rodents, the low-tech behavioral assays used most frequently have remained largely unchanged over the last several decades. The second set of experiments introduced and validated a novel behavioral task based on the classic measure of reward, conditioned place preference. In the modified test, objects rather than contexts were used as a conditioned cue, which potentially allows for greater flexibility and opens up new ways of analyzing conditioned approach, a commonly used measure for assessing the reward value of a given substance.