AMPA receptors mediate the pro-cognitive effects of electrical and optogenetic stimulation of the medial prefrontal cortex in antidepressant non-responsive Wistar–Kyoto rats

Autor: Magdalena Lason, Mariusz Papp, Paul Willner, Piotr Gruca, Ewa Litwa, W. Solecki
Rok vydání: 2020
Předmět:
Male
Deep Brain Stimulation
medicine.medical_treatment
Venlafaxine
Stimulation
Hippocampus
Rats
Inbred WKY
Depressive Disorder
Treatment-Resistant
Chronic mild stress
0302 clinical medicine
venlafaxine
Pharmacology (medical)
AMPA receptors
Prefrontal cortex
optogenetic stimulation
Behavior
Animal
Venlafaxine Hydrochloride
Wistar–Kyoto rat
Original Papers
deep brain stimulation
Psychiatry and Mental health
Antidepressive Agents
Second-Generation
Antidepressant
medicine.drug
Ampakine
Deep brain stimulation
medicine.drug_class
Wistar-Kyoto rat
Prefrontal Cortex
ampakine
AMPA receptor
Optogenetics
behavioral disciplines and activities
03 medical and health sciences
medicine
Animals
Excitatory Amino Acid Agents
Receptors
AMPA
Rats
Wistar
Pharmacology
business.industry
chronic mild stress
Rats
030227 psychiatry
Disease Models
Animal
nervous system
business
Neuroscience
medial prefrontal cortex
Stress
Psychological
030217 neurology & neurosurgery
Zdroj: Journal of Psychopharmacology (Oxford, England)
ISSN: 1461-7285
0269-8811
Popis: Background: The chronic mild stress (CMS) procedure is a widely used animal model of depression, and its application in Wistar–Kyoto (WKY) rats has been validated as a model of antidepressant-refractory depression. While not responding to chronic treatment with antidepressant drugs, WKY rats do respond to acute deep brain stimulation (DBS) of the medial prefrontal cortex (mPFC). In antidepressant-responsive strains there is evidence suggesting a role for AMPA subtype of glutamate receptor in the action mechanism of both antidepressants and DBS. Methods: Animals were subjected to CMS for 6 to 8 weeks; sucrose intake was monitored weekly and novel object recognition (NOR) test was conducted following recovery from CMS. Wistars were treated chronically with venlafaxine (VEN), while WKY were treated acutely with either DBS, optogenetic stimulation (OGS) of virally-transduced (AAV5-hSyn-ChR2-EYFP) mPFC or ventral hippocampus, or acute intra-mPFC injection of the AMPA receptor positive allosteric modulator CX-516. The AMPA receptor antagonist NBQX was administered, at identical sites in mPFC, immediately following the exposure trial in the NOR. Results: Sucrose intake and NOR were suppressed by CMS, and restored by VEN in Wistars and by DBS, OGS, or CX-516 in WKY. However, OGS of the ventral hippocampal afferents to mPFC was ineffective. A low dose of NBQX selectively blocked the procognitive effect of VEN, DBS and OGS. Conclusions: These results suggest that activation of AMPA receptors in the mPFC represents a common pathway for the antidepressant effects of both conventional (VEN) and novel (DBS, OGS) antidepressant modalities, in both antidepressant responsive (Wistar) and antidepressant-resistant (WKY) rats.
Databáze: OpenAIRE
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