Changes of benzodiazepine receptors during chronic benzodiazepine administration in humans

Changes of central type GABA(A)/benzodiazepine receptors during 24-day per- oral administration of alprazolam (2 mg/day) were measured with single phot on emission computed tomography (SPECT) in nine healthy human subjects. Rec eptor densities were measured on days -4 (baseline), 3, 10, 17 and 24. Comp arison of baseline and day 3 SPECT images was used to assess receptor occup ancy; comparisons of the four scans on medication were used to assess alter ations in receptor levels. Clinical effects were evaluated by subjective ra tings of mood and the Hopkins verbal learning test. Alprazolam induced seda tion associated with a 16% receptor occupancy. Unoccupied receptor levels d ecreased 10% from day 3 to day 10 but then normalized to baseline values by day 17. Clinical effects showed corresponding changes 1-2 weeks after the changes in the receptor. Thus, the decrease of benzodiazepine receptor dens ities may be one of the major mechanisms for tolerance development in human s. (C) 1999 Elsevier Science B.V. All rights reserved.