Animal Models Of Substance Use Disorders Research Articles

Neuroimmune modulators as novel pharmacotherapies for substance use disorders

One promising avenue of research is the use of neuroimmune modulators to treat substance use disorders (SUDs). Neuroimmune modulators target the interactions between the nervous system and immune system, which have been found to play a crucial role in the development and maintenance of SUDs. Multiple classes of substances produce alterations to neuroimmune signaling and peripheral immune function, including alcohol, opioids, and psychostimulants Preclinical studies have shown that neuroimmune modulators can reduce drug-seeking behavior and prevent relapse in animal models of SUDs. Additionally, early-phase clinical trials have demonstrated the safety and feasibility of using neuroimmune modulators as a treatment for SUDs in humans. These therapeutics can be used as stand-alone treatments or as adjunctive. This review summarizes the current state of the field and provides future directions with a specific focus on personalized medicine.

Effects of Beta Lactams on Behavioral Outcomes of Substance Use Disorders: A Meta-Analysis of Preclinical Studies

Introduction: Preclinical studies demonstrated that beta-lactams have neuroprotective effects in conditions involving glutamate neuroexcitotoxicity, including substance use disorders (SUDs). This meta-analysis aims to analyze the existing evidences on the effects of beta-lactams as glutamate transporter 1 (GLT-1) upregulators in animal models of SUDs, identification of gaps in the literature, and setting the stage for potential translation into clinical phases. Methods: Meta-analysis was conducted on preclinical studies retrieved systematically from MEDLINE and ScienceDirect databases. Abused substances were identified by refereeing to the National Institute on Drug Abuse (NIDA). The results were quantitatively described with a focus on the behavioral outcomes. Treatment effect sizes were described using standardized mean difference, and they were pooled using random effect model. I2-statistic was used to assess heterogeneity, and Funnel plot and Egger’s test were used for assessment of publication bias. Results: Literature search yielded a total of 71 studies that were eligible to be included in the analysis. Through these studies, the effects of beta-lactams were evaluated in animal models of nicotine, cannabis, amphetamines, synthetic cathinone, opioids, ethanol, and cocaine use disorders as well as steroids-related aggressive behaviors. Meta-analysis showed that treatments with beta-lactams consistently reduced the pooled undesired effects of the abused substances in several paradigms, including drug-self administration, conditioned place preference, drug seeking behaviors, hyperlocomotion, withdrawal syndromes, tolerance to analgesic effects, hyperalgesia, and hyperthermia. Conclusion: This meta-analysis revealed that enhancing GLT-1 expression in the brain through beta-lactams seemed to be a promising treatment approach in the context of substance use disorders, as indicated by results in animal models.

Ibogaine and addiction in the animal model, a systematic review and meta-analysis.

Ibogaine is a naturally occurring substance which has been increasingly used in the lay-scene to reduce craving and relapse in patients with substance use disorders (SUDs). Although human clinical trials on the safety and efficacy of ibogaine are lacking, animal studies do support the efficacy of ibogaine. In this systematic review and meta-analysis (MA), we summarise these animal findings, addressing three questions: (1) does ibogaine reduce addictive behaviour in animal models of SUDs?; (2) what are the toxic effects of ibogaine on motor functioning, cerebellum and heart rhythm?; (3) what are neuropharmacological working mechanisms of ibogaine treatment in animal models of SUDs? MA of 27 studies showed that ibogaine reduced drug self-administration, particularly during the first 24 h after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24 h after supplementation, and cerebral cell loss even weeks after administration. Data on ibogaines effect on cardiac rhythm, as well as on its neuropharmacological working mechanisms are limited. Our results warrant further studies into the clinical efficacy of ibogaine in SUD patients in reducing craving and substance use, but close monitoring of the patients is recommended because of the possible toxic effects. In addition, more work is needed to unravel the neuropharmacological working mechanisms of ibogaine and to investigate its effects on heart rhythm.

Animal Models and the Development of Vaccines to Treat Substance Use Disorders.

The development of pharmacotherapies for substance use disorders (SUDs) is a high priority in addiction research. At present, there are no approved pharmacotherapies for cocaine and methamphetamine use disorders, while treatments for nicotine and opioid use are moderately effective. Indeed, many of these treatments can cause adverse drug side effects and have poor medication compliance, which often results in increased drug relapse rates. An alternative to these traditional pharmacological interventions is immunotherapy or vaccines that can target substances associated with SUDs. In this chapter, we discuss the current knowledge on the efficacy of preclinical vaccines, particularly immunogens that target methamphetamine, cocaine, nicotine, or opioids to attenuate drug-induced behaviors in animal models of SUDs. We also review vaccines (and antibodies) against cocaine, nicotine, and methamphetamine that have been assessed in human clinical trials. While preclinical studies indicate that several vaccines show promise, these findings have not necessarily translated to the clinical population. Thus, continued effort to design more effective vaccine immunogens using SUD animal models is necessary in order to support the use of immunotherapy as a viable option for individuals with SUDs.