Background Studies of cocaine-dependent subjects have shown that re-ex
posure to environmental cues previously associated with cocaine use pr
oduces a strong conditioned response characterised by autonomic hypera
rousal and increases in subjective measures of cocaine craving. Method
s To evaluate the role of dopamine release by such cues, 20 cocaine-de
pendent inpatients were randomised in a single-dose, crossover, placeb
o-controlled design, to haloperidol (4 mg by mouth) and placebo. Plasm
a homovanillic acid (HVA, a dopamine metabolite), adrenocorticotropic
hormone (ACTH), and cortisol were assayed before and after cue exposur
e, Craving and anxiety were measured before and after cues with visual
analogue scales for desire to use cocaine now and for mood changes. F
indings Cocaine cues significantly increased anxiety, ACTH, cortisol,
and HVA. Increases in anxiety and craving resulting from cue exposure
were significantly antagonised by pretreatment with haloperidol. Inter
pretation It has long been hypothesised that increases in extracellula
r concentrations of dopamine mediate the acute reinforcing effects of
cocaine. Our data suggest that dopamine release may also mediate some
of the conditioned responses to cocaine cues.