Glucocorticoids and vulnerability to psychostimulant drugs: toward substrate and mechanism.

Glucocorticoid hormones can modulate the propensity of individuals to develop addictive behavior and, by doing so, contribute to the existence of individual differences in vulnerability to drugs. This article summarizes recent findings that increase our knowledge about drug-induced neuronal adaptations in the brain reward system and the role glucocorticoids may play in this process. Evidence exists that drugs and stress can induce similar changes in excitatory synaptic strength within the mesolimbic dopamine system, suggesting a coordinate mechanism for drugs of abuse and glucocorticoids. The glucocorticoid receptor (GR) plays an essential role in the stress-induced synaptic alterations, and studies using transgenic mice suggest that the GR is a key modulator of the motivation to take drugs and of the behavioral effects of repeated drug intake. The current state of research into the interplay between glucocorticoid hormones and addiction has reached a new phase in which detailed cellular and molecular analyses of the actual mechanisms will become possible. An important role is assigned to the GR, although many issues remain to be addressed, such as the actual site of glucocorticoid action in the brain, the molecular mechanisms and targets of GR-mediated glucocorticoid effects, and their interaction with genetic background.