Altered mRNA Levels of Stress-Related Peptides in Mouse Hippocampus and Caudate-Putamen in Withdrawal after Long-Term Intermittent Exposure to Tobacco Smoke or Electronic Cigarette Vapour.

Nicotine addiction is a severe public health problem. The aim of this study was to investigate the alterations in key neurotransmissions after 60 days of withdrawal from seven weeks of intermittent cigarette smoke, e-cigarette vapours, or an e-cigarette vehicle. In the nicotine withdrawal groups, increased depressive and anxiety/obsessive-compulsive-like behaviours were demonstrated in the tail suspension, sucrose preference and marble burying tests. Cognitive impairments were detected in the spatial object recognition test. A significant increase in Corticotropin-releasing factor (Crf) and Crf1 mRNA levels was observed, specifically after cigarette withdrawal in the caudate-putamen nucleus (CPu). The nociceptin precursor levels were reduced by cigarette (80%) and e-cigarette (50%) withdrawal in the CPu. The delta opioid receptor showed a significant reduction in the hippocampus driven by the exposure to an e-cigarette solubilisation vehicle, while the mRNA levels doubled in the CPu of mice that had been exposed to e-cigarettes. Withdrawal after exposure to e-cigarette vapour induced a 35% Bdnf mRNA decrease in the hippocampus, whereas Bdnf was augmented by 118% by cigarette withdrawal in the CPu. This study shows that long-term withdrawal-induced affective and cognitive symptoms associated to lasting molecular alterations in peptidergic signalling may determine the impaired neuroplasticity in the hippocampal and striatal circuitry.

A partial trace amine-associated receptor 1 agonist exhibits properties consistent with a methamphetamine substitution treatment.

Recent evidence suggests that the trace amine-associated receptor 1 (TAAR1) plays a pivotal role in the regulation of dopamine (DA) transmission and psychostimulant action. Several selective TAAR1 agonists have previously shown efficacy in models of cocaine addiction. However, the effects of TAAR1 activation on methamphetamine (METH)-induced behaviours are less well understood, as indeed are the underlying neurochemical mechanisms mediating potential interactions between TAAR1 and METH. Here, in a progressive ratio schedule of reinforcement the partial TAAR1 agonist, RO5263397, reduced the break-point for METH self-administration, while significantly increasing responding maintained by food reward. Following self-administration and extinction training, RO5263397 completely blocked METH-primed reinstatement of METH seeking. Moreover, when used as a substitute, unlike a low dose of METH, which sustained vigorous responding when substituting for the training dose of METH, RO5263397 was not self-administered at any dose, thus exhibiting no apparent abuse liability. Fast-scan cyclic voltammetry experiments showed that RO5263397 prevented METH-induced DA overflow in slices of the nucleus accumbens, while having no effect on DA transmission in its own right. Collectively, the present observations demonstrate that partial TAAR1 activation decreases the motivation to self-administer METH, blocks METH-primed reinstatement of METH seeking and prevents METH-induced DA elevations in the nucleus accumbens, and strongly support the candidacy of TAAR1-based medications as potential substitute treatment in METH addiction.

Is online shopping addiction still a depressive illness? -- the induced consumption and traffic trap in live E-commerce.

While immersive shopping has injected new vitality into China's e-commerce, it has also resulted in consumers' over-reliance on online shopping. Psychological studies have linked online shopping addiction with depression, but business practices challenge this conclusion. This study, grounded in addiction theory, developed a theoretical model, and conducted an online survey with 214 live-streaming shoppers using structural equation modeling for validation. The primary focus was on determining whether consumers truly become addicted to online shopping in the four stages of the addiction model. The study unveils the process of consumers becoming addicted to online shopping. It explores the moderating role of perceived risk in the relationship between utilitarian and hedonic purchases and online shopping addiction. The findings suggest that through tactics such as traffic promotion, traffic trapping, anchor feature utilization, and incorporation of consumer aesthetics, merchants may induce utilitarian and hedonic purchases, leading to addiction to live-streaming shopping among consumers. Furthermore, perceived risk significantly and negatively moderates the relationship between utilitarian purchases and online shopping addiction. Our research indicates that merchants intentionally create external stimuli, enticing consumers to indulge in online shopping, suggesting that online shopping addiction is not merely a simple psychological state but may be influenced by external factors. This study provides novel insights into the phenomenon of online shopping addiction while offering valuable recommendations for consumers seeking to avoid succumbing to its allure.

National Institute on Drug Abuse genomics consortium white paper: Coordinating efforts between human and animal addiction studies.

The National Institute on Drug Abuse Genetics and Epigenetics Cross-Cutting Research Team convened a diverse group of researchers, clinicians, and healthcare providers on the campus of the University of California, San Diego, in June 2018. The goal was to develop strategies to integrate genetics and phenotypes across species to achieve a better understanding of substance use disorders through associations between genotypes and addictive behaviors. This conference (a) discussed progress in harmonizing large opioid genetics cohorts, (b) discussed phenotypes that are used for genetics studies in humans, (c) examined phenotypes that are used for genetics studies in animal models, (d) identified synergies and gaps in phenotypic analyses of human and animal models and (e) identified strategies to integrate genetics and genomics data with phenotypes across species. The meeting consisted of panels that focused on phenotype harmonization (Dr. Laura Bierut, Dr. Olivier George, Dr. Dan Larach and Dr. Sesh Mudumbai), translating genetic findings between species (Dr. Elissa Chesler, Dr. Gary Peltz and Dr. Abraham Palmer), interpreting and understanding allelic variations (Dr. Vanessa Troiani and Dr. Tamara Richards) and pathway conservation in animal models and human studies (Dr. Robert Hitzemann, Dr. Huda Akil and Dr. Laura Saba). There were also updates that were provided by large consortia (Dr. Susan Tapert, Dr. Danielle Dick, Dr. Howard Edenberg and Dr. Eric Johnson). Collectively, the conference was convened to discuss progress and changes in genome-wide association studies.

Understanding Addiction Using Animal Models.

Drug addiction is a neuropsychiatric disorder with grave personal consequences that has an extraordinary global economic impact. Despite decades of research, the options available to treat addiction are often ineffective because our rudimentary understanding of drug-induced pathology in brain circuits and synaptic physiology inhibits the rational design of successful therapies. This understanding will arise first from animal models of addiction where experimentation at the level of circuits and molecular biology is possible. We will review the most common preclinical models of addictive behavior and discuss the advantages and disadvantages of each. This includes non-contingent models in which animals are passively exposed to rewarding substances, as well as widely used contingent models such as drug self-administration and relapse. For the latter, we elaborate on the different ways of mimicking craving and relapse, which include using acute stress, drug administration or exposure to cues and contexts previously paired with drug self-administration. We further describe paradigms where drug-taking is challenged by alternative rewards, such as appetitive foods or social interaction. In an attempt to better model the individual vulnerability to drug abuse that characterizes human addiction, the field has also established preclinical paradigms in which drug-induced behaviors are ranked by various criteria of drug use in the presence of negative consequences. Separation of more vulnerable animals according to these criteria, along with other innate predispositions including goal- or sign-tracking, sensation-seeking behavior or impulsivity, has established individual genetic susceptibilities to developing drug addiction and relapse vulnerability. We further examine current models of behavioral addictions such as gambling, a disorder included in the DSM-5, and exercise, mentioned in the DSM-5 but not included yet due to insufficient peer-reviewed evidence. Finally, after reviewing the face validity of the aforementioned models, we consider the most common standardized tests used by pharmaceutical companies to assess the addictive potential of a drug during clinical trials.

Effect of the Novel Positive Allosteric Modulator of Metabotropic Glutamate Receptor 2 AZD8529 on Incubation of Methamphetamine Craving After Prolonged Voluntary Abstinence in a Rat Model.

BACKGROUND: Cue-induced methamphetamine craving increases after prolonged forced (experimenter-imposed) abstinence from the drug (incubation of methamphetamine craving). Here, we determined whether this incubation phenomenon would occur under conditions that promote voluntary (self-imposed) abstinence. We also determined the effect of the novel metabotropic glutamate receptor 2 positive allosteric modulator, AZD8529, on incubation of methamphetamine craving after forced or voluntary abstinence. METHODS: We trained rats to self-administer palatable food (6 sessions) and then to self-administer methamphetamine under two conditions: 12 sessions (9 hours/day) or 50 sessions (3 hours/day). We then assessed cue-induced methamphetamine seeking in extinction tests after 1 or 21 abstinence days. Between tests, the rats underwent either forced abstinence (no access to the food- or drug-paired levers) or voluntary abstinence (achieved via a discrete choice procedure between methamphetamine and palatable food; 20 trials per day) for 19 days. We also determined the effect of subcutaneous injections of AZD8529 (20 and 40 mg/kg) on cue-induced methamphetamine seeking 1 day or 21 days after forced or voluntary abstinence. RESULTS: Under both training and abstinence conditions, cue-induced methamphetamine seeking in the extinction tests was higher after 21 abstinence days than after 1 day (incubation of methamphetamine craving). AZD8529 decreased cue-induced methamphetamine seeking on day 21 but not day 1 of forced or voluntary abstinence. CONCLUSIONS: We introduce a novel animal model to study incubation of drug craving and cue-induced drug seeking after prolonged voluntary abstinence, mimicking the human condition of relapse after successful contingency management treatment. Our data suggest that positive allosteric modulators of metabotropic glutamate receptor 2 should be considered for relapse prevention.