A Neuro-anatomical Model

Altered stress systems progressively impact on dopaminergic networks to cause the neuro-anatomical “brain signatures” of addiction (17).

Reward – stress prgressively activates the dorsal striatum (DS) (87) and substance-related cues elicit dopamine release in DS (88) in line with addiction severity, suggesting the strengthening of substance-related habits as addiction progresses. This reflects a shift in reward processing from the ventral striatum (VS) to DS.

Stress and dopamine are both involved in habit learning (89, 90).  Lesions to the DS dopamine prevent habit formation (91).

Memory – elevated stress triggers excessive engagement of habitual processes, by changing the role of memory systems in behaviour. For example, acute stress before a learning task results in a predominantly habitual rather than a cognition-based role of memory in task completion (35). Or switches to DS implicit from the hippocampal-related explicit memory system.

Chronic stress causes opposing structural changes in neural networks subserving goal-directed and habitual action, with prefrontal cortex (PFC) atrophy and DS hypertrophy (35). Bias toward habitual responding after chronic stress may accelerate these transitions from initially goal-directed to habitual and compulsive action with reduced cognitive control interacting with overshooting stress reactivity to influence the progression from initial drug use to addiction.

Glococorticoids (GCs) may act in concert with noradrenaline (NE) to shift instrumental action from goal-directed to habitual (93-95).

Behaviour control – post mortem analyses show changes in the neurochemistry of the PFC following chronic drug abuse, with impaired PFC and enhanced DS. GCs can act as a switch between these two memory systems in behaviour prompting and modulate a DS-based habit system over the PFC-based goal-directed system thus rendering behaviour habitual rather than goal-directed. This is accompanied by reduced explicit knowledge of action-outcome associations which may contribute insight into why addicts relapse despite often being aware of the negative consequences (96-100).

Emotion – emotional regulation, via an “emotional arousal habit bias”activated by chronic amgydaloid activity, may also become DS dependent.

We propose a similar cascade as proposed by Koob and Volkow (and discussed by Everitt and Robbins); a cascade of neuroadaptations from the VS to DS with dysregulation of the PFC, cingulate gyrus, and amygdala (22).

At the heart of this transition is the amgydaloid region.  During the addiction cycle, increased release of catecholamines (dopamine and NE) and GCs progressively strengthen amygdaloid functions, such as the consolidation of emotionally relevant information, whilst weakening PFC functioning and emotional regulation (33). The resultant amgydaloid hyperactivity impairs hippocampal function (and explicit memory) with the basolateral amgydala (BLA) modulating recruitment of habit memory (35). OFC/VM PFC dysfunction may also affect this amgydaloid hyperactivity (50) alongside hippocampal dysfunction.

Catecholamine dysfunction may also render the PFC “offline” and facilitate this shift to DS-based control of behaviour, via habitual emotional responses of the amygdala (101).  As addiction becomes chronic, emotional responding to internal stress becomes habitualised and increasingly under automatic striatal control, via a compulsive “emotional arousal habit bias” (49).

Thus, to summarise, transition to DS-prompted behaviour may involve dysregulation of PFC, ACC and BLA/hippocampus under increasing levels of stress/emotional distress with various neuro-anatomical ‘switches’  facilitating this process, in the shift from stress-based wanting to compulsion, see Figure 2.

In effect amgydala hyperactivity renders behaviour compulsive by recruiting the dorsal striatum in effect, reward, and memory processes.

Reward is dealt with automatically, memory becomes implicit (thus drastically reducing awareness in explicit memory of negative consequences) affect, becomes distress based and also automatically recruits the compulsive responding of the dorsal striatum. Distress thus becomes a stimulus for automatic responding.

Fig 2

1. Prefrontal Cortex control of behaviour “switches” to more compulsive, automatic control of behaviour via overshooting stress reactivity of the addiction cycle.

2. ACC hypofunctioning acts as a “switch” between conscious, cognitive/cortical control to unconscious, automatic dorsal striatal and between explicit and implicit memory systems – during stress and emotion dysregulation.

3. Hippocampal-dependent memory is also ‘switched’ to DS-dependent memory via the modulatory influence of BLA projections of stress chemicals  – also the consequence of stress and emotion dysregulation.

4. Reward processing from VS to DS.  Increasing emotional distress also act as a stimulus to the response of compulsive addictive behaviours.

References (to follow)