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Kranz et al.: Intrinsic Activity, 2013; 1(Suppl. 1):A4.6
published online: 1 October 2013
Joint Meeting of the Austrian Neuroscience Association (13th ANA Meeting) and the Austrian Pharmacological Society (19th Scientific Symposium of APHAR) Vienna, Austria, 16–19 September 2013 Furthermore, our study reveals a strong dependence of regional SSRI-induced occupancy of the serotonin transporter
SERT blockage and residual availability on pretreatment SERT investigated with positron emission tomography
availability. These findings corroborate sustained SERT binding and Georg S. Kranz1, Rupert Lanzenberger1,*, Daniela Haeusler2, Pia rebinding of SSRIs in regions with high SERT availability as Baldinger1, Markus Savli1, Marie Spies1, Gregor Gryglewski1, mechanisms of prolonged antidepressant drug action [3]. Wolfgang Wadsak2, Markus Mitterhauser2 and Siegfried Kasper1 References
1Department of Psychiatry and Psychotherapy, Medical University of 1. Meyer JH, Wilson AA, Sagrati S, Hussey D, Carella A, Potter WZ, Vienna, Austria; 2Department of Biomedical Imaging and Image- Ginovart N, Spencer EP, Cheok A, Houle S: Serotonin transporter
guided Therapy, Division of Nuclear Medicine, Medical University of occupancy of five selective serotonin reuptake inhibitors at
different doses: an [11C]DASB positron emission tomography
study. Am J Psychiatry, 2004; 161(5):826–835.
Background: According to the law of mass action, and assuming
2. Gill JS, Zezulka AV, Beevers DG, Davies P: Relation between
that serotonin transporter (SERT) availability is proportional to its initial blood pressure and its fall with treatment. Lancet, 1985;
density, SERT occupancy by selective serotonin reuptake inhibitors (SSRIs), defined as percent signal reduction should be similar 3. Vauquelin G, Charlton SJ: Long-lasting target binding and
across regions. However, an earlier positron emission tomography rebinding as mechanisms to prolong in vivo drug action.
(PET) study found SERT occupancies to vary across regions [1]. Br J Pharmacol, 2010; 161(3):488–508. We therefore tested the homogeneity of regional SERT occupancy and its dependence on pretreatment SERT availability in depressed
Methods: Nineteen out-patients suffering from major depression
received oral doses of either escitalopram (10 mg/day, 10 subjects)
or citalopram (20 mg/day, 9 subjects) (Lundbeck A/S, Denmark) and
underwent one [11C]DASB PET scan before treatment (PET1) and
one 6 hours following the first SSRI dose (PET2). SERT binding
potential (BPND) was quantified and occupancy was defined as:
occupancy (%) = (1 − BPND PET2 / BPND PET1) × 100. Regional SERT
occupancies were compared to mean occupancies across regions.
Associations between SERT occupancy and pretreatment
availability were tested using two different approaches to avoid
statistical artefacts [2]: (i) regression of residual SERT availability on
pretreatment availability; (ii) correlation of the mean between
pretreatment and residual availability (Oldham’s transformation) and
absolute SERT reduction.
Results: Occupancies at PET2 ranged between 43.53 ± 18.09 %
and 82.16 ± 7.36 %. Mean cortical occupancy values were
significantly lower than mean subcortical occupancy values
(65.66 ± 10.60 % vs. 72.99 ± 6.75 %, p = 0.001, paired samples
t-test). Repeated-measures ANOVA and post-hoc paired samples
t-tests revealed that middle and inferior temporal cortex had
significantly lowered occupancies, whereas subgenual cingulate
cortex had significantly greater occupancies compared to mean
cortical occupancies. Likewise, subcortical regions such as the
putamen and thalamus, exhibited decreased occupancies, whereas
amygdala and raphe nuclei had greater occupancies compared to
mean subcortical occupancies (all p < 0.05 corrected). Regression
analysis revealed a strong positive effect of pretreatment SERT
binding on residual SERT binding (R2 = 0.92, β = 0.96, T = 15.10,
p < 0.001). Similarly, high associations were found between
Oldham’s transformation and absolute change after treatment
across brain regions (r = 0.99, p < 0.001). That is, regions with
higher baseline SERT BPND were significantly more occupied by
acute SSRI treatment.
Discussion: Our results indicate regional differences in SERT
occupancy associated with acute treatment with SSRIs.
_______________________________ *Corresponding author e-mail:  2013 Intrinsic Activity, ISSN 2309-8503; Austrian Pharmacological Society (APHAR) page 1 of 1 (not for citation purpose)


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