Effect of chemogenetic modulation of hippocampal neurons on depression and spatial memory impairment in a rat model for temporal lobe epilepsy.
-
1
Department of Head and Skin, Ghent University, Belgium
-
2
Department of Neurosciences, KU Leuven, Belgium
-
3
Vrije University Brussel, Belgium
RATIONALE
Major depression and spatial memory impairment are the most common comorbidities in patients with temporal lobe epilepsy (TLE). For these patients, treatment options are limited highlighting the need for innovative treatments such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Studies investigating the effect of DREADDs on these comorbidities are lacking.
In the present study, we evaluated whether activation of hM4Di DREADDs with clozapine affects anhedonia (i.e. the inability to experience pleasure) and spatial memory in the intraperitoneal kainic acid (IPKA) rat model for TLE.
METHOD
Status epilepticus (SE) was elicited by i.p. kainic acid (KA) injections in male Sprague Dawley rats. A control group was injected with saline (SAL). Three months post-SE, animals received bilateral intrahippocampal adeno-associated viral vector injections (2x0.5µL) carrying the hM4Di DREADD or a SHAM construct, yielding four experimental groups: KA-DREADD (n=8), KA-SHAM (n=6), SAL-DREADD (n=5) and SAL-SHAM (n=5). Anhedonia was evaluated using the saccharin preference test (SPT) and the novel object test (NOL) to assess spatial memory impairment. Following hM4Di DREADDs activation by clozapine (0.1 mg/kg, s.c.), the SPT and NOL were repeated.
RESULTS
The KA group showed a significant reduction in preference towards saccharin compared to the SAL group (66.25% vs 96.96% respectively, p<0.001). In the NOL, a trend towards spatial memory impairment was observed in the KA group. DREADDs activation with clozapine increased preference towards saccharin in the KA-DREADD group, while spatial memory was not affected compared to SHAM groups.
CONCLUSION
The IPKA rat model displays anhedonic-like behavior whereas enlargement of sample size is required for characterization of spatial memory impairment. Although activation of hM4Di DREADDs did not alter spatial memory, an increased preference towards saccharin was present in the IPKA rat model containing hM4Di DREADDs, suggesting a potential antidepressant effect.
Keywords:
Epilepsy,
DREADDs,
spatial memory,
Depression,
chemogenetics
Conference:
13th National Congress of the Belgian Society for Neuroscience , Brussels, Belgium, 24 May - 24 May, 2019.
Presentation Type:
Poster presentation
Topic:
Behavioral/Systems Neuroscience
Citation:
Craey
E,
Goossens
M,
Desloovere
J,
Merckx
C,
Van Den Haute
C,
Baekelandt
V,
De Bundel
D,
Smolders
IJ,
Vonck
K,
Boon
P and
Raedt
R
(2019). Effect of chemogenetic modulation of hippocampal neurons on depression and spatial memory impairment in a rat model for temporal lobe epilepsy..
Front. Neurosci.
Conference Abstract:
13th National Congress of the Belgian Society for Neuroscience .
doi: 10.3389/conf.fnins.2019.96.00072
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
23 Apr 2019;
Published Online:
27 Sep 2019.
*
Correspondence:
PhD. Erine Craey, Department of Head and Skin, Ghent University, Ghent, East Flanders, Belgium, erine.craey@ugent.be