Synaptic Sabotage

Synaptic Sabotage 2022 Amrita Rehal American Class of 2023 Acrylic on Canvas There exist natural stimuli with positive survival value that are both rewarding and reinforcing such as food and sex. Physiological states and learned associations increase the incentive salience of a reward and related cues. This is mediated by dopaminergic systems in the brain. Some pharmacological agents possess highly potent rewarding properties that result in rapid learning of predictive cues, motivating drug seeking. Our inclination for survival has perfected our brain’s learning and memory systems to seek out rewarding behaviors; addictive drugs and behaviors tap into existing mechanisms of reward-related learning and become overvalued at the expense of other rewards, harming the organism. Rewarding effects of drugs are associated with a fast and steep release of dopamine (DA) from neurons in the Ventral Tegmental Area (VTA) that project to various areas, notably the Nucleus Accumbens (NAcc). Both natural and drug-related rewards increase synaptic DA in the NAcc, and this assigns incentive salience to the reward and related cues, triggering “wanting”, or motivation, critical to reward-related learning. Conditioned responses to drugs and related cues are enduring, remaining measurable after long periods of abstinence. The persistence of addiction results from the persistence of associative memory stored as physiological changes in synaptic connections and even alterations in gene expression. Addictive drugs may trigger synaptic plasticity in the VTA and its targets, enhancing its rewarding and motivational effects by increasing the synaptic strength of excitatory DA neurons and producing sensitized incentive salience. Over the backdrop of our brain’s billions of neurons, we see a representation of those that subject us to pathological drug seeking, where synaptic potentiation in DA neurons has occurred in the VTA. Addictions such as those of nicotine, alcohol, opiates, and gambling are visualized as synapses saturated with DA in the synaptic cleft. These neurons exhibit strengthened synaptic connections contributing to addiction. Although an over-simplification, this is symbolic in understanding how our neurons are “sabotaged” to become perfectly attuned to associations, cues, contexts, and rewards of these very addictive stimuli. It is our own marvelous brains that not only ensure our survival but are also thus vulnerable to “hijacking” by addictive drugs and behaviors that exploit our adaptive neuroplasticity. Addiction is pervasive within in our society, yet a lack of education contributes to stigmas and social ostracism that depict addicts as less human. This work serves to highlight the beauty and importance of our brain\u27s learning and memory mechanisms and the powerful, enduring control over this natural circuitry that certain drugs and behaviors can have. https://www.annualreviews.org/doi/10.1146/annurev.neuro.29.051605.113009 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135092