The role of cortisol suppression on craving for and satisfaction from nicotine in high and low impulsive subjects.

The rewarding properties of drug self-administration have been shown to depend on mesolimbic dopamine release but also on the availability of corticosterone, as shown in rats. Since this became particularly evident when tested in rat strains bred for high (HR) and low (LR) reactivity to novel stimuli, the role of cortisol and personality in drug craving was investigated in 60 male nicotine-deprived smokers divided according to questionnaire scores into high and low impulsives, a dimension considered to represent HR/LR rats. They either received the peripheral cortisol blocker metyrapone (MET) or the centrally blocking substance dexamethasone (DEX) or placebo (n=20 each) and were then allowed to smoke. MET more than DEX reduced craving for cigarettes during deprivation. This was only observed in low impulsives while high impulsives developed low craving unmodified by blockade of cortisol. Satisfaction from smoking was less achieved with DEX than with MET and not modified by impulsivity. Differences between MET and DEX in influencing craving during deprivation and satisfaction from smoking were discussed on the basis of different glucocorticoid receptors. The mineralocorticoid receptor (MR) seems to be the 'turn on switch' and the glucocorticoid receptor (GR) the 'turn off switch' in mediating the rewarding properties of dopamine in drug self-administration. Copyright 2002 John Wiley & Sons, Ltd.