This review presents some of the work that has been carried out to investigate the behavioural effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-receptor antagonists in animal models of substance abuse. Many of the studies have been conducted in light of current ideas that emphasise the analogous role of glutamatergic mechanisms in synaptic plasticity and long-term behavioural adaptation to drugs. Experiments on behavioural sensitisation indicate that whereas N-methyl-D-aspartate receptors are involved in induction, AMPA-receptors may mediate expression of the established response. In this regard, an important factor may be the degree of drug-environment conditioning. Thus, studies of the effects of AMPA-receptor antagonists on conditioned behaviours are reviewed here. Relatively few studies on the effects of AMPA-receptor antagonists on primary reinforcement from self-administered drugs and the subjective effects of drugs have been carried out, but a profile that contrasts with that of the N-methyl-D-aspartate antagonists appears to be emerging. Studies of withdrawal from opioids suggest that whilst AMPA-receptor antagonists may not be able to prevent tolerance or dependence from developing, they may ameliorate both the physical and emotional consequences of withdrawal. Overall, the AMPA-receptor antagonists may represent a promising new approach for treating the consequences of drug abuse. However, as results are often complicated by the use of the less-selective compounds, it will be important to use better tools in future studies.