Interaction Between Stress and Addiction: Contributions From Latin-American Neuroscience

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.

CB1R activation in nucleus accumbens core promotes stress-induced reinstatement of cocaine seeking by elevating extracellular glutamate in a drug-paired context

“…Stressful life events are an important factor that increases the risk of relapse to drug use in humans, since they can be harmful, uncontrollable and often unavoidable in everyday life 1 , 2 . This scenario has been modeled in rodents using different associative learning paradigms, such as self-administration and conditioned place preference (CPP), to induce ‘reinstatement’ of drug-seeking behavior through exposure to different stressors 3 , 4 . Consistent with a large body of research on therapeutic strategies for cocaine addiction 5 , different pharmacological treatments that target the glutamatergic system were able to prevent stress-induced reinstatement 6 – 9 .…”

Dopamine Axon Targeting in the Nucleus Accumbens in Adolescence Requires Netrin-1

“…FIGURE 1 | Netrin-1 levels in the nucleus accumbens (NAcc) vary across postnatal life. (A) Sagittal section of an adolescent mouse brain showing the mesolimbic system, composed of dopamine projection neurons that innervate the NAcc and the mesocortical circuitry, that innervate the prefrontal cortex (PFC) (image adapted fromTorres-Berrio et al, 2018). Mesolimbic dopamine axons are already present in the NAcc while mesocortical dopamine axons continue to grow to the PFC across the adolescent period.…”

Consumo de substâncias psicoativas pelos estudantes de medicina e sua relação com o programa de mentoria

“…Contudo, não podemos afirmar quais são os fatores associados a esse quadro, embora seja reconhecida a presença do estresse no ambiente acadêmico 21 e a relação entre esse e o abuso de álcool. 22,23 Por outro lado, o abuso de outras drogas foi maior no ciclo básico do curso, talvez por ser uma fase de experimentação como apontado por outro estudo. 17 Também não podemos descartar a influência do meio e outras características da personalidade, como busca por novidades, que influenciam a tomada de decisão do jovem diante da experimentação das drogas.…”