Addiction is a chronic, relapsing disorder characterized by compulsive substance use despite adverse consequences. This chapter reviews neurotransmitters and neural pathways across the three stages of addiction: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Dopamine drives reinforcement and habit formation during early use, with endogenous opioids, endocannabinoids, and serotonin modulating hedonic and emotional aspects of motivation; corticotropin-releasing factor, dynorphin, and norepinephrine mediate the dysphoria and stress sensitivity that sustain dependence; and glutamate and GABA dysregulation in prefrontal-striatal circuits underlies cue-induced craving and relapse vulnerability. Together, these adaptations illustrate how the same neurotransmitter systems that evolved to support learning, motivation, and survival are co-opted by repeated drug exposure to produce familiar clinical phenomena in substance use disorders. Understanding these mechanisms informs treatment strategies targeting reinforcement, stress, and executive function in parallel. Framing addiction through this neurobiological lens reduces stigma, shifting perceptions from moral weakness to maladaptive plasticity in otherwise adaptive brain systems.

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Neurotransmitters and Neural Pathways

  • Julia Steigerwald Schnall

摘要

Addiction is a chronic, relapsing disorder characterized by compulsive substance use despite adverse consequences. This chapter reviews neurotransmitters and neural pathways across the three stages of addiction: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Dopamine drives reinforcement and habit formation during early use, with endogenous opioids, endocannabinoids, and serotonin modulating hedonic and emotional aspects of motivation; corticotropin-releasing factor, dynorphin, and norepinephrine mediate the dysphoria and stress sensitivity that sustain dependence; and glutamate and GABA dysregulation in prefrontal-striatal circuits underlies cue-induced craving and relapse vulnerability. Together, these adaptations illustrate how the same neurotransmitter systems that evolved to support learning, motivation, and survival are co-opted by repeated drug exposure to produce familiar clinical phenomena in substance use disorders. Understanding these mechanisms informs treatment strategies targeting reinforcement, stress, and executive function in parallel. Framing addiction through this neurobiological lens reduces stigma, shifting perceptions from moral weakness to maladaptive plasticity in otherwise adaptive brain systems.