Abstract
Drug addiction is a chronic neuropsychiatric disorder that escalates from an initial exposure to drugs of abuse, such as cocaine, cannabis, or heroin, to compulsive drug-seeking and intake, reduced ability to inhibit craving-induced behaviors, and repeated cycles of abstinence and relapse. It is well-known that chronic changes in the brain’s reward system play an important role in the neurobiology of addiction. Notably, environmental factors such as acute or chronic stress affect this system, and increase the risk for drug consumption and relapse. Indeed, the HPA axis, the autonomic nervous system, and the extended amygdala, among other brain stress systems, interact with the brain’s reward circuit involved in addictive behaviors. There has been a growing interest in studying the molecular, cellular, and behavioral mechanisms of stress and addiction in Latin-America over the last decade. Nonetheless, these contributions may not be as strongly acknowledged by the broad scientific audience as studies coming from developed countries. In this review, we compile for the first time a series of studies conducted by Latin American-based neuroscientists, who have devoted their careers to studying the interaction between stress and addiction, from a neurobiological and clinical perspective. Specific contributions about this interaction include the study of CRF receptors in the lateral septum, investigations on the neural mechanisms of cross-sensitization for psychostimulants and ethanol, the identification of the Wnt/β-catenin pathway as a critical neural substrate for stress and addiction, and the emergence of the cannabinoid system as a promising therapeutic target. We highlight animal and human studies, including for instance, reports coming from Latin American laboratories on single nucleotide polymorphisms in stress-related genes and potential biomarkers of vulnerability to addiction, that aim to bridge the knowledge from basic science to clinical research.
Highlights
Drug addiction is a chronic neuropsychiatric disorder characterized by the compulsive intake of drugs of abuse and the loss of control over this consumption, in spite of the devastating consequences it carries for the individual (American Psychiatric Association, 2013)
In Latin America, the geographical region that comprises a part of North America (Mexico), Central America, South America, and the Caribbean, there is a strong association between drug use and having a history of violence, sexual abuse, and other stressful and traumatic events (Montoya et al, 2003; Alegría et al, 2004; Vera et al, 2005; Alvarez et al, 2007; Tucci et al, 2010; Frade et al, 2013; SAMHSA, 2016)
Vega-Quiroga et al (2018), showed that stimulation of the lateral septum (LS) increased DA levels in the ventral tegmental area (VTA) by innervating GABAergic interneurons and decreasing GABA-induced inhibition of DA neurons (Vega-Quiroga et al, 2018). These results demonstrate that stress determines DA levels in the LS and VTA in response to cocaine by regulating corticotropin-releasing factor (CRF) binding on CRF receptor type 1 (CRFR1)
Summary
Drug addiction is a chronic neuropsychiatric disorder characterized by the compulsive intake of drugs of abuse and the loss of control over this consumption, in spite of the devastating consequences it carries for the individual (American Psychiatric Association, 2013). Human imaging and preclinical studies indicate that addiction involves maladaptive changes in the brain’s reward system that result from complex gene–environment interactions (Sweitzer et al, 2012; Walker and Nestler, 2018) Environmental factors such as early exposure to drugs or chronic stress facilitate the acquisition and maintenance of drug-related behaviors in vulnerable individuals, and are strong predictors of addiction relapse (Saal et al, 2003). We report the different contributions made by Latin American researchers who study the molecular and cellular role of stress in drug abuse and addiction using rodent behavioral models. The use of animal models has become a tremendous tool for studying drug-associated behaviors and deciphering the molecular mechanisms underlying the long-term effects of exposure to drugs Different paradigms such as behavioral drug sensitization, CPP, and self-administration have been developed to study drug-reward, craving, and relapse in rodents. We will discuss the remarkable work of Latin American neuroscientists who make use of these behavioral models to understand the neurobiological mechanisms of addiction
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