Regional brain volume changes following chronic antipsychotic administration are mediated by the dopamine D2 receptor.

Neuroimage 2018 08 26;176:226-238. Epub 2018 Apr 26.

Department of Psychiatry & Integrated Program in Neuroscience, McGill University, 845 Sherbrooke St W, Montreal, QC, H3A 0G4 Canada; Sorbonne University, Neuroscience Paris Seine, CNRS UMR 8246, INSERM U 1130, UPMC Univ Paris 06, UM119, 75005, Paris, France. Electronic address:

Background: Neuroanatomical alterations are well established in patients suffering from schizophrenia, however the extent to which these changes are attributable to illness, antipsychotic drugs (APDs), or their interaction is unclear. APDs have been extremely effective for treatment of positive symptoms in major psychotic disorders. Their therapeutic effects are mediated, in part, through blockade of D2-like dopamine (DA) receptors, i.e. the D2, D3 and D4 dopamine receptors. Furthermore, the dependency of neuroanatomical change on DA system function and D2-like receptors has yet to be explored.

Methods: We undertook a preclinical longitudinal study to examine the effects of typical (haloperidol (HAL)) and atypical (clozapine (CLZ)) APDs in wild type (WT) and dopamine D2 knockout (D2KO) mice over 9-weeks using structural magnetic resonance imaging (MRI).

Results: Chronic typical APD administration in WT mice was associated with reductions in total brain (p = 0.009) and prelimbic area (PL) (p = 0.02) volumes following 9-weeks, and an increase in striatal volume (p = 0.04) after six weeks. These APD-induced changes were not present in D2KOs, where, at baseline, we observed significantly smaller overall brain volume (p < 0.01), thinner cortices (q < 0.05), and enlarged striata (q < 0.05). Stereological assessment revealed increased glial density in PL area of HAL treated wild types. Interestingly, in WT and D2KO mice, chronic CLZ administration caused more limited changes in brain structure.

Conclusions: Our results present evidence for the role of D2 DA receptors in structural alterations induced by the administration of the typical APD HAL and that chronic administration of CLZ has a limited influence on brain structure.

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S10538119183036
Publisher Site
http://dx.doi.org/10.1016/j.neuroimage.2018.04.054DOI Listing
August 2018
17 Reads

Publication Analysis

Top Keywords

dopamine receptors
8
brain volume
8
blockade d2-like
4
effects mediated
4
type dopamine
4
mediated blockade
4
d2-like dopamine
4
volumes 9-weeks
4
receptors dopamine
4
wild type
4
dependency neuroanatomical
4
receptors dependency
4
p = 002 volumes
4
therapeutic effects
4
disorders therapeutic
4
positive symptoms
4
increase striatal
4
striatal volume
4
treatment positive
4
knockout d2ko
4

Similar Publications