Abstract
The allostatic theory of drug abuse describes the brain’s reward system alterations as substance misuse progresses. Neural adaptations arising from the reward system itself and from the antireward system provide the subject with functional stability, while affecting the person’s mood. We propose a computational hypothesis describing how a virtual subject’s drug consumption, cognitive substrate, and mood interface with reward and antireward systems. Reward system adaptations are assumed interrelated with the ongoing neural activity defining behavior toward drug intake, including activity in the nucleus accumbens, ventral tegmental area, and prefrontal cortex (PFC). Antireward system adaptations are assumed to mutually connect with higher-order cognitive processes occurring within PFC, orbitofrontal cortex, and anterior cingulate cortex. The subject’s mood estimation is a provisional function of reward components. The presented knowledge repository model incorporates pharmacokinetic, pharmacodynamic, neuropsychological, cognitive, and behavioral components. Patterns of tobacco smoking exemplify the framework’s predictive properties: escalation of cigarette consumption, conventional treatments similar to nicotine patches, and alternative medical practices comparable to meditation. The primary outcomes include an estimate of the virtual subject’s mood and the daily account of drug intakes. The main limitation of this study resides in the 21 time-dependent processes which partially describe the complex phenomena of drug addiction and involve a large number of parameters which may underconstrain the framework. Our model predicts that reward system adaptations account for mood stabilization, whereas antireward system adaptations delineate mood improvement and reduction in drug consumption. This investigation provides formal arguments encouraging current rehabilitation therapies to include meditation-like practices along with pharmaceutical drugs and behavioral counseling.
Highlights
The principle of allostasis was established to enhance the homeostatic model whereby the well-balanced functional state of a living being is sustained by the constant conservation of the organism’s inner environment
We propose a computational hypothesis describing how a virtual subject’s drug consumption, cognitive substrate, and mood interface with reward and antireward systems
The initial conditions of the presented simulations are defined by 71 parameters whose values, reported in Table S1 in Supplementary Material, are chosen according to Ref. [8] and [12] with few exceptions: where possible, parameters defining the simulations were chosen according to human studies
Summary
The principle of allostasis was established to enhance the homeostatic model whereby the well-balanced functional state of a living being is sustained by the constant conservation of the organism’s inner environment. The allostatic model advances that the internal state of the organism continuously adapts to the surrounding natural world, attaining functional stability through the adaptation of physiological thresholds [1]. As defined by Sterling and Eyer, “allostasis provides for continuous re-evaluation of need and for continuous readjustment of all parameters toward new setpoints” [1]. In humans, this continuous adaptation to the environment is reached by means of neural and endocrine processes that are able to take priority over homeostatic regulations [1]. The present paper is concerned with understanding and modeling the role of allostasis in drug addiction
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