Effects of Methamphetamine Self-Administration and Extinction on Astrocyte Structure and Function in the Nucleus Accumbens Core

B. M. Siemsen, C. M. Reichel, K. C. Leong, C. Garcia-Keller, Cassandra Gipson-Reichardt, S. Spencer, J. A. McFaddin, K. N. Hooker, P. W. Kalivas, M. D. Scofield

Research output: Contribution to journalArticle

Abstract

Astrocytes provide support for neurons, regulate metabolic processes, and influence neuronal communication in a variety of ways, including through the homeostatic regulation of glutamate. Following 2-h cocaine or methamphetamine self-administration (SA) and extinction, rodents display decreased levels of basal glutamate in the nucleus accumbens core (NAcore), which transitions to elevated glutamate levels during drug seeking. We hypothesized that, like cocaine, this glutamate ‘overflow’ during methamphetamine seeking arises via decreased expression of the astroglial glutamate transporter GLT-1, and withdrawal of perisynaptic astroglial processes (PAPs) from synapses. As expected, methamphetamine self-administration and extinction decreased the level of contact made by PAPs in the NAcore, yet did not impact glutamate uptake, GLT-1 expression, or the general structural characteristics of astrocytes. Interestingly, systemic administration of N-acetylcysteine (NAC), a drug that both upregulates GLT-1 and promotes glial-glutamate release, reduced cued methamphetamine seeking. In order to test the impact of astrocyte activation and the induction of glial glutamate release within the NAcore, we employed astrocyte-specific expression of designer receptors exclusively activated by designer drugs (DREADDs). We show here that acute activation of Gq-coupled DREADDs in this region inhibited cued methamphetamine seeking. Taken together, these data indicate that cued methamphetamine seeking following two-hour SA is not mediated by deficient glutamate clearance in the NAcore, yet can be inhibited by engaging NAcore astrocytes.

Original languageEnglish (US)
Pages (from-to)528-541
Number of pages14
JournalNeuroscience
Volume406
DOIs
StatePublished - May 15 2019

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Self Administration
Methamphetamine
Nucleus Accumbens
Astrocytes
Glutamic Acid
Designer Drugs
Cocaine
Neuroglia
Amino Acid Transport System X-AG
Psychological Extinction
Acetylcysteine
Pharmaceutical Preparations
Synapses
Rodentia
Up-Regulation
Communication
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Effects of Methamphetamine Self-Administration and Extinction on Astrocyte Structure and Function in the Nucleus Accumbens Core. / Siemsen, B. M.; Reichel, C. M.; Leong, K. C.; Garcia-Keller, C.; Gipson-Reichardt, Cassandra; Spencer, S.; McFaddin, J. A.; Hooker, K. N.; Kalivas, P. W.; Scofield, M. D.

In: Neuroscience, Vol. 406, 15.05.2019, p. 528-541.

Research output: Contribution to journalArticle

Siemsen, BM, Reichel, CM, Leong, KC, Garcia-Keller, C, Gipson-Reichardt, C, Spencer, S, McFaddin, JA, Hooker, KN, Kalivas, PW & Scofield, MD 2019, 'Effects of Methamphetamine Self-Administration and Extinction on Astrocyte Structure and Function in the Nucleus Accumbens Core', Neuroscience, vol. 406, pp. 528-541. https://doi.org/10.1016/j.neuroscience.2019.03.040
Siemsen, B. M. ; Reichel, C. M. ; Leong, K. C. ; Garcia-Keller, C. ; Gipson-Reichardt, Cassandra ; Spencer, S. ; McFaddin, J. A. ; Hooker, K. N. ; Kalivas, P. W. ; Scofield, M. D. / Effects of Methamphetamine Self-Administration and Extinction on Astrocyte Structure and Function in the Nucleus Accumbens Core. In: Neuroscience. 2019 ; Vol. 406. pp. 528-541.
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