differential sensitivity to alcohol, anxiety predisposition, panic disorder and stress responsiveness (see Fig. 3 ). Genetically determined factors may also lead to different positions of the set-point (see also benzodiazepine dependence). Recent evidence suggests that the benzodiazepine receptor spectrum is not fixed and that the 'set-point' -- where drugs bind, but have no effect -- can be moved. Anxiety states, particularly panic disorder, may be due to receptor abnormalities which lead to a movement of the set-point in the inverse agonist direction. ANXIETY: A BENZODIAZEPINE RECEPTOR ABNORMALITY? Evidence that anxiety disorders may be caused by abnormalities in benzodiazepine receptors has come from a series of studies using the benzodiazepine receptor antagonist, flumazenil, both as a challenge test and as an imaging ligand. When patients with panic disorder were given an intravenous 2 mg dose of flumazenil, enough to occupy more than half of the receptors in the brain, it provoked panic in most of the patients but was quite innocuous in the control subjects ( Nutt et al , 1990 ). This finding, which has been replicated in a number of studies (though not in all) ( Woods et al , 1991 ; Maddock, 1998 ; Strohle et al , 1999 ) clearly demonstrates that panic disorder is not due to the actions of an inverse agonist, as in this case the antagonisit would reduce anxiety. The anxiogenic effect of flumazenil could reflect displacement of an endogenous agonist, but this would only be present in patients (since controls did not