The Neurobiological Basis of Addiction – From Choice to Habit to Compulsion

Researchers used male Lister Hooded rats that underwent functional disconnections (by excitotoxic lesions) of the amygdala-striatal networks, combined with cocaine self-administration training sessions. Measurements at different stages (early, intermediate and late) of goal-directed, cue-controlled cocaine-seeking behaviour were analysed to understand the effect of disconnections on habit formation and maintenance.

Manipulations of the amygdala-striatal network in Lister Hooded rats actually showed that the BLA and the central nucleus of the amygdala (CeN) were required to initially recruit the aDLS in the establishment of dopamine-dependent cocaine-seeking habits in these rats.

However, once cocaine-seeking behaviour was established (i.e. habitual), inactivation of the BLA did not affect maintenance of cocaine-seeking behaviour. In fact, these habits were dependent on the functional connection between the CeN and aDLS. If the CeN was functionally disconnected, there was a dramatic reduction in the maintenance of established cocaine-seeking habits.

This research uncovers a novel neural circuit that would explain why chronic cocaine exposure results in involuntary and compulsive cocaine-seeking behaviour. In the establishment of any substance addiction, the BLA indirectly controls the aDLS through the NA. However, this new data suggests that chronic addiction causes a functional transition that directly links the amygdala to the aDLS. The end result is a robust and functional network that links motivational drug-associated environmental cues with a persistent and compulsive drug-seeking habit.

Addiction is a psychiatric disorder of which there are many theories on the interaction of the neurobiological mechanisms of aberrant learning and memory behaviour. However, it is strongly argued that addiction results from the pathological hypersensitisation of both drug-associated stimuli and drug-induced effects.

This pathologically compulsive behaviour is also exacerbated by changes in the prefrontal cortex—the region of the brain where decision-making and inhibitory control is governed. Chronic exposure to drugs progressively manipulates the prefrontal cortex until decision-making and judging the consequence of one’s own actions becomes difficult.

Treatment for chronic drug addicts presently involves cognitive behavioural therapy that attempts to breakdown the connection between emotional impulses and habitual behaviour. However, this new research would suggest that individuals who are compulsively addicted might not even be aware of the motivational cues and the subsequent impulsive actions that these cues elicit.

Volkow and colleagues used brain imaging (PET scans) to study how drugs affect dopamine levels in the brains of addicted individuals. They discovered that addicted individuals had reduced dopamine increases compared to non-addicted individuals when exposed to drugs.

Surprisingly, addicted individuals showed higher dopamine increases in response to cues associated with drug cravings than to the actual drug itself. The researchers suggested that this difference contributes to chronic substance use, as individuals keep using drugs in an attempt to achieve the expected reward despite blunted effects.

Furthermore, addicted individuals in early or protracted withdrawal have lower levels of D2 receptors in specific brain regions. These lower D2 receptor levels are linked to reduced activity in frontal brain regions responsible for decision-making and control. This disruption in brain activity leads to compulsive and impulsive behaviours, increasing the risk of drug reinstatement or relapse during withdrawal.

This study provides clear evidence that there is a functionally independent neural network that maintains drug-seeking behaviour in long-term drug addiction.

This new understanding of the interaction between the CeN and the aDLS in the control of addiction may aid the development of treatments that target compulsive drug-seeking behaviour.