Search
Serotonergic–Muscarinic Interaction within the Prefrontal Cortex as a Novel Target to Reverse Schizophrenia-Related Cognitive Symptoms
Abstract
Recent studies revealed that the activation of serotonergic 5-HT1A and muscarinic M1, M4, or M5 receptors prevent MK-801-induced cognitive impairments in animal models. In the present study, the effectiveness of the simultaneous activation of 5-HT1A and muscarinic receptors at preventing MK-801-induced cognitive deficits in novel object recognition (NOR) or Y-maze tests was investigated. Activators of 5-HT1A (F15599), M1 (VU0357017), M4 (VU0152100), or M5 (VU0238429) receptors administered at top doses for seven days reversed MK-801-induced deficits in the NOR test, similar to the simultaneous administration of subeffective doses of F15599 (0.05 mg/kg) with VU0357017 (0.15 mg/kg), VU0152100 (0.05 mg/kg), or VU0238429 (1 mg/kg). The compounds did not prevent the MK-801-induced impairment when administered acutely. Their activity was less evident in the Y-maze. Pharmacokinetic studies revealed high brain penetration of F15599 (brain/plasma ratio 620%), which was detected in the frontal cortex (FC) up to 2 h after administration. Decreases in the brain penetration properties of the compounds were observed after acute administration of the combinations, which might have influenced behavioral responses. This negative effect on brain penetration was not observed when the compounds were administered repeatedly. Based on our results, prolonged administration of a 5-HT1A activator with muscarinic receptor ligands may be effective at reversing cognitive decline related to schizophrenia, and the FC may play a critical role in this interaction.
Citations
-
8
CrossRef
-
0
Web of Science
-
8
Scopus
Authors (5)
-
Paulina Cieślik
-
Adrianna Radulska
-
Grzegorz Burnat
-
Joanna M. Wierońska
Cite as
Full text
- Publication version
- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms22168612
- License
-
open in new tab
Keywords
Details
- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
-
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
no. 22,
ISSN: 1661-6596 - Language:
- English
- Publication year:
- 2021
- Bibliographic description:
- Cieślik P., Radulska A., Burnat G., Kalinowski L., Wierońska J. M.: Serotonergic–Muscarinic Interaction within the Prefrontal Cortex as a Novel Target to Reverse Schizophrenia-Related Cognitive Symptoms// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES -Vol. 22,iss. 16 (2021), s.8612-
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms22168612
- Verified by:
- Gdańsk University of Technology
seen 95 times
Recommended for you
Procognitive activity of nitric oxide inhibitors and donors in animal models
- P. Cieślik,
- L. Kalinowski,
- J. M. Wierońska
Neurochemical changes underlying cognitive impairment in olfactory bulbectomized rats and the impact of the mGlu5-positive allosteric modulator CDPPB
- A. Płoska,
- P. Cieślik,
- A. Siekierzycka
- + 2 authors
Dysfunctional prefrontal cortical network activity and interactions following cannabinoid receptor activation.
- M. T. Kucewicz,
- M. D. Tricklebank,
- R. Bogacz
- + 1 authors