Archival ReportEffect of Chronic Antipsychotic Treatment on Brain Structure: A Serial Magnetic Resonance Imaging Study with Ex Vivo and Postmortem Confirmation
Section snippets
Animals
Male Sprague-Dawley rats (Charles River UK, Ltd., Kent, United Kingdom), initial body weight 240 g to 250 g (9 weeks of age) were housed four per cage under a 12-hour light/dark cycle (7:00 am lights on) with food and water available ad libitum. Room temperature was maintained at 21 ± 2°C and relative humidity at 55 ± 10%. Animals were habituated for 7 days before experimental procedures. Animal experiments were carried out with local ethical approval and in accordance with the Home Office
Plasma Levels and Behavior
Administration of APD by osmotic pump achieved plasma levels (mean ± SD) of 20.58 ± 1.99 ng/mL for HAL and 60.13 ± 20.75 ng/mL for OLZ, respectively. The emergence of VCMs in both HAL and OLZ treated animals by 2 weeks confirmed animals were responding to the APD (Figure 2). However, there was poor correlation (Spearman's ρ = .112; ns) between drug plasma levels and VCM behavior at 8 weeks. The dosing regimen used in this study was tailored to capture clinical practice, i.e., OLZ with a median
Discussion
This is the first in vivo longitudinal study in rodents demonstrating that chronic (8 weeks) APD treatment results in altered brain morphology. We observed a decrease in WBV and CTX volume in rats chronically treated with therapeutically relevant doses of either HAL or OLZ (40, 41). Exposure to either drug resulted in similar reductions in brain volumes, compared with vehicle-treated animals, the magnitude of these effects being 6% to 8% on WBV and 8% to 12% on CTX volume, respectively. The
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Authors ACV and SN contributed equally to this work.