Inhibition of fatty acid amide hydrolase reverses aberrant prefrontal gamma oscillations in the sub-chronic PCP model for schizophrenia
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F24%3A43921284" target="_blank" >RIV/00023752:_____/24:43921284 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s00221-024-06801-2" target="_blank" >https://link.springer.com/article/10.1007/s00221-024-06801-2</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00221-024-06801-2" target="_blank" >10.1007/s00221-024-06801-2</a>
Alternative languages
Result language
angličtina
Original language name
Inhibition of fatty acid amide hydrolase reverses aberrant prefrontal gamma oscillations in the sub-chronic PCP model for schizophrenia
Original language description
Hypofunctioning of NMDA receptors, and the resulting shift in the balance between excitation and inhibition, is considered a key process in the pathophysiology of schizophrenia. One important manifestation of this phenomenon is changes in neural oscillations, those above 30 Hz (i.e., gamma-band oscillations), in particular. Although both preclinical and clinical studies observed increased gamma activity following acute administration of NMDA receptor antagonists, the relevance of this phenomenon has been recently questioned given the reduced gamma oscillations typically observed during sensory and cognitive tasks in schizophrenia. However, there is emerging, yet contradictory, evidence for increased spontaneous gamma-band activity (i.e., at rest or under baseline conditions). Here, we use the sub-chronic phencyclidine (PCP) rat model for schizophrenia, which has been argued to model the pathophysiology of schizophrenia more closely than acute NMDA antagonism, to investigate gamma oscillations (30–100 Hz) in the medial prefrontal cortex of anesthetized animals. While baseline gamma oscillations were not affected, oscillations induced by train stimulation of the posterior dorsal CA1 (pdCA1) field of the hippocampus were enhanced in PCP-treated animals (5 mg/kg, twice daily for 7 days, followed by a 7-day washout period). This effect was reversed by pharmacological enhancement of endocannabinoid levels via systemic administration of URB597 (0.3 mg/kg), an inhibitor of the catabolic enzyme of the endocannabinoid anandamide. Intriguingly, the pharmacological blockade of CB1 receptors by AM251 unmasked a reduced gamma oscillatory activity in PCP-treated animals. The findings are consistent with the observed effects of URB597 and AM251 on behavioral deficits reminiscent of the symptoms of schizophrenia and further validate the potential for cannabinoid-based drugs as a treatment for schizophrenia.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Experimental Brain Research
ISSN
0014-4819
e-ISSN
1432-1106
Volume of the periodical
242
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
1149-1160
UT code for WoS article
001185788500001
EID of the result in the Scopus database
2-s2.0-85187947010