A12 Addiction (sensitization of the reward circuit)

Title

The addiction model extends the phasic dopaminergic signaling of the reward circuit (extension of E4 synaptic transmission) induced by an addictive substance or stimulus. Repeated exposure produces progressive sensitization of the dopaminergic system (in the same functional manner as the sensitization described in A7), while in parallel pharmacological tolerance develops due to homeostatic adaptation of the receptors (extension of the D desensitization state of E10), which reduces the net hedonic response despite maintaining or increasing the dose. The allostatic theory of addiction also postulates a progressive drift of the basal hedonic set point, whose deficit with respect to the original value manifests clinically as craving. These changes are consolidated by reinforced synaptic plasticity in the VTA-nucleus accumbens circuit, using the same functional form of Hebb's rule defined in E7.

ID:4294