Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development.
Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development.
Pharmacol Rev. 2021 Jan;73(1):163-201
Authors: Koob GF
Abstract
Compulsive drug seeking that is associated with addiction is hypothesized to follow a heuristic framework that involves three stages (binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation) and three domains of dysfunction (incentive salience/pathologic habits, negative emotional states, and executive function, respectively) via changes in the basal ganglia, extended amygdala/habenula, and frontal cortex, respectively. This review focuses on neurochemical/neurocircuitry dysregulations that contribute to hyperkatifeia, defined as a greater intensity of negative emotional/motivational signs and symptoms during withdrawal from drugs of abuse in the withdrawal/negative affect stage of the addiction cycle. Hyperkatifeia provides an additional source of motivation for compulsive drug seeking via negative reinforcement. Negative reinforcement reflects an increase in the probability of a response to remove an aversive stimulus or drug seeking to remove hyperkatifeia that is augmented by genetic/epigenetic vulnerability, environmental trauma, and psychiatric comorbidity. Neurobiological targets for hyperkatifeia in addiction involve neurocircuitry of the extended amygdala and its connections via within-system neuroadaptations in dopamine, enkephalin/endorphin o...
Source: Pharmacological Reviews - Category: Drugs & Pharmacology Authors: Koob GF Tags: Pharmacol Rev Source Type: research
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