From liking to wanting to craving: changes in neural circuitry that drive addiction

Alcohol dependence, along with other addictions, is a neuropsychiatric disorder. One aspect of this pathology is the conditioning whereby cues associated with drug use can themselves acquire the power to control behaviour and contribute to relapse. With the wonder of functional magnetic resonance imaging (fMRI) this process can – literally – be seen in the brain.

In light drinkers, exposure to alcohol-related stimuli causes activation in the ventral part of the striatum. In heavy social drinkers – some of whom were dependent – activation occurred in the dorsal part of the striatum. And reduced activation of the ventral region correlated with increasing scores on a new scale measuring compulsive drinking.

fMRI studies undertaken by Dr Sabine Vollstädt-Klein (Mannheim/Heidelberg University, Germany) show that patients who drink while being unaware of drinking  have reduced responsiveness to alcohol-related cues in the ventral tegmental area. So what we are seeing in dependence seems to be automated substance consumption, of the kind suggested by Everitt and Robbins, with reduced activation of reward-related centres.

Evidence suggests that prefrontal control seen in non-dependent drinkers is lost as dependence develops, and is replaced by striatal control. Functional changes in limbic and sensorimotor circuits – and a shift towards the latter -- seem to underlie the development of dependence as drug use moves from recreational, hedonic, goal-related behaviour through habitual use to dysregulated escalation and compulsion.

If a shift from prefrontal to striatal control accompanies the development of alcohol dependence, a crucial question is whether brain circuits can be reset in patients “dry” for long periods. It may be possible to reverse abnormal circuitry by cue exposure training. But the implication is that this can take a long time, and patients who have been through this process also relapse, Dr Vollstädt-Klein noted.

The results of this alcohol strand of addiction research complement animal experiments and clinical studies of cocaine users. These suggest that there is a transition from ventral to dorsal striatum with cocaine also, though this occurs surprisingly early in the natural history of use of the drug.

Dopamine (DA) signalling seems to be intimately involved in CNS changes in both alcohol and cocaine abuse, and there is some evidence that manipulation of the DA system can influence drug-seeking behaviour. If so, there are potentially useful implications for the harm-reduction approach to alcohol problems. 

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.