Archival ReportGq-DREADD Selectively Initiates Glial Glutamate Release and Inhibits Cue-induced Cocaine Seeking
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Animal Housing and Surgery
All procedures were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and the Association for the Assessment and Accreditation of Laboratory Animal Care International. Male Sprague Dawley rats (250 g to 300 g on arrival; Charles River Laboratories, Wilmington, Massachusetts) were individually housed in a temperature- and humidity-controlled environment with a 12-hour dark/light cycle. Experiments were conducted during the animals׳
Astrocyte-Specific Expression of Gq-DREADD
Injection of the GFAP-Gq-DREADD virus in the NAcore produced fields of transduced astrocytes, easily distinguished from neurons given their morphology and lack of co-localization with a NeuN neuronal marker (Figure 1A,B). The GFAP-Gq-DREADD virus produced an immunoreactivity pattern consistent with astrocyte labeling (30, 31, 32), and astrocyte-specific expression of Gq-DREADD was very likely given the apparent co-localization of the astrocyte-specific filament protein GFAP and viral HA signals
Discussion
Our data demonstrate that Gq-DREADD-mediated enhancement of NAcore glial-glutamate release was SNARE-dependent and that the inhibitory effect of glial-glutamate on reinstated cocaine seeking was mediated by mGluR2/3. Several groups have shown that activation of Gq-DREADD elevates [Ca2+]i, potentially leading to enhanced gliotransmission (21, 34). Here, we show that activating Gq-DREADD in NAcore astrocytes promotes the release of glutamate. In support, hippocampal studies reveal a parallel
Acknowledgments and Disclosures
This research was supported by Grants from the National Institutes of Health to PWK (R015369 and DA003906). MDS was also partially supported by a National Institute on Drug Abuse Training Grant (T32 DA 7288-22).
The authors report no biomedical financial interests or potential conflicts of interest.
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