The Neurobiological Basis of Addiction – From Choice to Habit to Compulsion
Time to read: 3 minutes
Addiction is a chronic neurological disorder that involves the limbic cortico-striatal neural networks of the brain. During chronic drug exposure, there is a progressive neurobiological adaptation that promotes a loss of control over drug-seeking behaviour. Cocaine use, for example, is initially, for many, a voluntary choice that develops into a habitual goal-directed behaviour and progresses to compulsive cocaine seeking, despite serious negative consequences to the user.
In the beginning, it is the nucleus accumbens (NA) in the ventral striatum and its functional interaction with the basolateral amygdala (BLA) that are responsible for developing voluntary cocaine-seeking behaviour. The NA plays an important role in dopamine-dependent reward circuits that turn motivation into action, while the BLA provides positive consolidation of cocaine-associated memories with environmental cues.
Continued exposure to cocaine, however, causes neurobiological adaptations in the striatum, with control over cocaine-seeking habits passing to the anterior dorsolateral striatum (aDLS). This functional shift in neural control, from habitual to compulsive drug-seeking behaviour, is greatly influenced by drug-associated Pavlovian conditioned stimuli that induce drug-cravings and even relapses after abstinence.
However, the neural mechanisms that underlie this transition to long-term, compulsive drug seeking are unclear. To answer this, researchers from the University of Cambridge and the University of Poitiers have analysed amygdala-striatal circuits in rats that were trained to seek cocaine in an attempt to understand how long-term maintenance of maladaptive cocaine-seeking habits develop.
WHO AND WHAT WAS STUDIED?
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.
WHAT WERE THE FINDINGS?
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.
WHAT DOES THE STUDY REALLY TELL US?
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.
THE BIG PICTURE
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.
WHAT SHOULD I KNOW?
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.
QUIZ
References
Murray et al., Basolateral and central amygdala differentially recruit and maintain dorsolateral striatum-dependent cocaine-seeking habits, Nature Communications, 6:10088, December 2015