8.1.2 - Biological addiction explanations

Reward and neuroadaptation

A biological explanation connects the action of a drug with changes in brain signalling, motivation and adaptation.

Recall that a neurotransmitter carries a signal between neurons and a receptor responds to particular chemical signals. An agonist activates a receptor; an antagonist prevents or reduces its activation. The general synaptic process is taught in Biological psychology; here we apply it to three drugs.

One important reward pathway connects the ventral tegmental area (VTA) with the nucleus accumbens. Dopamine signalling contributes to learning which events are rewarding or important and to motivation to repeat actions associated with them. Dopamine is not a complete “pleasure chemical” explanation: pleasure, motivation, memory, stress and control involve interacting systems.

Drugs can alter this signalling by different routes. Repeated exposure can produce neuroadaptation, changes in how nervous-system activity responds to the drug. These changes help explain tolerance and dependence. Withdrawal and reduced reward from ordinary activities can then motivate further use. Biological accounts explain why a drug can reinforce behaviour, but the existence of a reward pathway does not mean everyone exposed will develop addiction. NIAAA's neuroscience resource presents addiction as changes across reward, stress and control circuits rather than a single dopamine event.

Alcohol mode of action

Alcohol affects several signalling systems rather than acting only at one receptor type.

In a simplified account, alcohol enhances inhibitory GABA signalling and reduces excitatory glutamate signalling, including signalling through NMDA receptors. Inhibition makes a neuron less likely to fire; excitation makes firing more likely. Shifting this balance helps explain alcohol's sedating and coordination-impairing effects. Alcohol also increases dopamine signalling in reward pathways indirectly, so rewarding effects can encourage repetition. Its effects depend on concentration, brain region and the individual; “depressant” does not mean that every behaviour must become less active.

With repeated heavy exposure, the nervous system develops compensatory changes opposing alcohol's effects. Less response to a familiar amount contributes to tolerance. When alcohol is removed, the adapted system can become overexcitable, helping explain anxiety, tremor and other withdrawal effects. Drinking to relieve these effects can maintain dependence. The NICE alcohol guideline's pharmacology account explains the GABA/glutamate balance and its relevance to withdrawal.

This mechanism predicts that acute reward and later relief of withdrawal can both motivate drinking. It does not predict that every drinker becomes addicted, nor does it establish that all alcohol problems result from one fixed neurotransmitter imbalance. Learning, stress, opportunities and social context influence the pathway from exposure to harmful continued use.

Heroin mode of action

Heroin is an opioid whose active metabolites stimulate opioid receptors and alter pain and reward signalling.

Heroin enters the brain and is converted into active metabolites, including morphine. These act as agonists at mu-opioid receptors, mimicking some actions of the body's endogenous opioids. This contributes to pain relief and rewarding effects. In an important reward-circuit account, opioid action reduces activity in inhibitory GABA neurons that normally restrain dopamine neurons in the VTA. Reducing that restraint is disinhibition: dopamine-neuron activity and dopamine signalling towards the nucleus accumbens can increase.

The causal chain matters. An inhibitory cell is inhibited, so its target is less inhibited. It is therefore possible for an opioid with inhibitory actions at particular cells to increase dopamine signalling downstream. The drug does not simply “add dopamine”, and opioid receptors are not dopamine receptors. NIDA's opioid-receptor research monograph establishes the active-metabolite and mu-receptor account.