Unbalanced neuronal circuits in addiction

Abstract

Through sequential waves of drug-induced neurochemical stimulation, addiction co-opts the brain's neuronal circuits that mediate reward, motivation to behavioral inflexibility and a severe disruption of self-control and compulsive drug intake. Brain imaging technologies have allowed neuroscientists to map out the neural landscape of addiction in the human brain and to understand how drugs modify it.

Figure 1

A carefully balance set of interconnected functional modules instantiates the processing of myriad and competing signals, including reward, expectation, saliency, motivation, value learning, emotional value, ambiguity, conflict, and cognitive processing that underlie decision making and ultimately our ability to exert free will. Many extrinsic and intrinsic factors (triggers), acting upon a variety of intermediary systems (mediators), can perturb the balance among the system of circuits in charge of orchestrating adaptive goal directed behaviors.

Figure 2

Fronto-striatal circuitry of stimulus-response habits. A. Schematic anatomical representation of the mesocorticolimbic dopamine system in the human brain, highlighting several key processing stations: Ventral Tegmental Area (VTA) and Substantia Nigra (SN), Nucleus Accumbens (NAc) in the ventral striatum, Thalamus and Subthalamic Nuclei, and Prefrontal cortex, among others. Modified with permission [15]. B. Four of the frontostriatal cortical circuits that appear to play major roles in executive functioning and inhibitory control. DL: dorsolateral; DM: dorsomedial; VA: ventroanterior; VM: ventromedial; r: right; IFG: inferior frontal gyrus; preSMA: pre somatic motor area; STN: sub-thalamic nucleus. Modified with permission [28].

Figure 3

Schematic depiction of dopaminergic control of positive and negative motivation loops in the dorsal striatum. A. When an action results in a better-than-predicted situation, DA neurons fire a burst of spikes, which is likely to activate D1Rs on direct pathway neurons and facilitate immediate action and corticostriatal plasticity changes that make it more likely to select that action in the future. B. In contrast, when the result of an action is worse-than-expected, DA neurons are inhibited reducing DA, which is likely to inhibit D2Rs indirect pathway neurons, suppressing immediate action and the reinforcement of corticostriatal synapses, leading to suppression of that action in the future. Reprinted with permission [101].