TY - JOUR
T1 - Effects of chronic exposure to haloperidol, olanzapine or lithium on SV2A and NLGN synaptic puncta in the rat frontal cortex
AU - Halff, Els F
AU - Cotel, Marie-Caroline
AU - Natesan, Sridhar
AU - McQuade, Richard
AU - Ottley, Chris J
AU - Srivastava, Deepak P
AU - Howes, Oliver D
AU - Vernon, Anthony C
N1 - Funding Information:
We would like to thank George Chennell and Chen Liang of the Wohl Cellular Imaging Centre (King's College London) for their technical assistance with confocal imaging. ACV acknowledges financial support for this study from the Medical Research Council (New Investigator Research Grant (NIRG), MR/N025377/1). The work (at King's College, London) was also supported by the Medical Research Council (MRC) Centre grant (MR/N026063/1).
Funding Information:
ACV acknowledges financial support for this study from the Medical Research Council (New Investigator Research Grant (NIRG) , MR/N025377/1) . The work (at King’s College, London) was also supported by the Medical Research Council (MRC) Centre grant ( MR/N026063/1) .
Publisher Copyright:
© 2021 Elsevier B.V.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5/7
Y1 - 2021/5/7
N2 - Positron emission tomography studies using the synaptic vesicle glycoprotein 2A (SV2A) radioligand [11C]-UCB-J provide in vivo evidence for synaptic dysfunction and/or loss in the cingulate and frontal cortex of patients with schizophrenia. In exploring potential confounding effects of antipsychotic medication, we previously demonstrated that chronic (28-day) exposure to clinically relevant doses of haloperidol does not affect [3H]-UCB-J radioligand binding in the cingulate and frontal cortex of male rats. Furthermore, neither chronic haloperidol nor olanzapine exposure had any effect on SV2A protein levels in these brain regions. These data do not exclude the possibility, however, that more subtle changes in SV2A may occur at pre-synaptic terminals, or the post-synaptic density, following chronic antipsychotic drug exposure. Moreover, relatively little is known about the potential effects of psychotropic drugs other than antipsychotics on SV2A. To address these questions directly, we herein used immunostaining and confocal microscopy to explore the effect of chronic (28-day) exposure to clinically relevant doses of haloperidol, olanzapine or the mood stabilizer lithium on presynaptic SV2A, postsynaptic Neuroligin (NLGN) puncta and their overlap as a measure of total synaptic density in the rat prefrontal and anterior cingulate cortex. We found that, under the conditions tested here, exposure to antipsychotics had no effect on SV2A, NLGN, or overall synaptic puncta count. In contrast, chronic lithium exposure significantly increased NLGN puncta density relative to vehicle, with no effect on either SV2A or total synaptic puncta. Future studies are required to understand the functional consequences of these changes.
AB - Positron emission tomography studies using the synaptic vesicle glycoprotein 2A (SV2A) radioligand [11C]-UCB-J provide in vivo evidence for synaptic dysfunction and/or loss in the cingulate and frontal cortex of patients with schizophrenia. In exploring potential confounding effects of antipsychotic medication, we previously demonstrated that chronic (28-day) exposure to clinically relevant doses of haloperidol does not affect [3H]-UCB-J radioligand binding in the cingulate and frontal cortex of male rats. Furthermore, neither chronic haloperidol nor olanzapine exposure had any effect on SV2A protein levels in these brain regions. These data do not exclude the possibility, however, that more subtle changes in SV2A may occur at pre-synaptic terminals, or the post-synaptic density, following chronic antipsychotic drug exposure. Moreover, relatively little is known about the potential effects of psychotropic drugs other than antipsychotics on SV2A. To address these questions directly, we herein used immunostaining and confocal microscopy to explore the effect of chronic (28-day) exposure to clinically relevant doses of haloperidol, olanzapine or the mood stabilizer lithium on presynaptic SV2A, postsynaptic Neuroligin (NLGN) puncta and their overlap as a measure of total synaptic density in the rat prefrontal and anterior cingulate cortex. We found that, under the conditions tested here, exposure to antipsychotics had no effect on SV2A, NLGN, or overall synaptic puncta count. In contrast, chronic lithium exposure significantly increased NLGN puncta density relative to vehicle, with no effect on either SV2A or total synaptic puncta. Future studies are required to understand the functional consequences of these changes.
UR - http://www.scopus.com/inward/record.url?scp=85101725677&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2021.113203
DO - 10.1016/j.bbr.2021.113203
M3 - Article
C2 - 33636238
SN - 0166-4328
VL - 405
SP - 113203
JO - Behavioural brain research
JF - Behavioural brain research
M1 - 113203
ER -