A12 Addiction (sensitization of the reward circuit)

Topic

The reward circuit normally responds to pleasurable stimuli through phasic dopaminergic signaling—a pattern of brief, intense dopamine release. An addictive substance or stimulus can trigger this same phasic dopaminergic signaling within the reward circuit; when exposure to that substance or stimulus is repeated over time, the reward circuit undergoes two parallel changes that jointly determine the circuit's net hedonic response—that is, the amount of pleasure ultimately produced by each exposure.

The first of these two parallel changes is the progressive sensitization of the reward circuit's dopaminergic system: the more frequently exposure to the addictive substance or stimulus is repeated, the more intense the reward circuit's dopaminergic response becomes with each new exposure, following the same pattern of progressive sensitization previously described for the dopaminergic system in another psychiatric model.

The second change, developing in parallel within the same reward circuit, is pharmacological tolerance: the reward circuit's dopamine receptors undergo homeostatic adaptation to repeated exposure and become progressively less sensitive to dopamine. The more frequently exposure to the addictive substance or stimulus is repeated, the greater this pharmacological tolerance becomes; this tolerance reduces the reward circuit's net hedonic response, even when the substance dosage remains constant or increases.

According to the allostatic theory of addiction, the reduction in the reward circuit's net hedonic response—resulting from this balance between sensitization and tolerance—has an additional, slower-developing consequence: the reward circuit's baseline hedonic set point (the level of pleasure the circuit considers normal in the absence of the substance) progressively shifts downward with each exposure episode. The greater the deficit between this shifted baseline hedonic set point and its original value, the more intense the craving experienced by the individual—that intense, hard-to-control desire to consume the substance or seek the addictive stimulus.

All these changes—ranging from dopaminergic sensitization to the shift in the baseline hedonic set point—become consolidated through reinforced synaptic plasticity within the reward circuit, specifically the pathway connecting the ventral tegmental area to the nucleus accumbens. This process follows the associative learning principle known as Hebb's rule, which has previously been used to describe the strengthening of synaptic connections in other models. Ultimately, this reinforced synaptic plasticity is what durably locks into the reward circuit the dopaminergic sensitization, pharmacological tolerance, and shift in the baseline hedonic set point that characterize addiction.

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