Drug-Induced Plasticity Contributing to Heightened Relapse Susceptibility: Neurochemical Changes and Augmented Reinstatement in High-Intake Rats

Authors

Aric Madayag, Marquette UniversityFollow
Kristen S. Kau, Marquette UniversityFollow
Doug Lobner, Marquette UniversityFollow
John R. Mantsch, Marquette UniversityFollow
Samantha Wisniewski, Marquette University
David A. Baker, Marquette UniversityFollow

Document Type

Article

Language

eng

Publication Date

1-6-2010

Publisher

Society for Neuroscience

Source Publication

The Journal of Neuroscience

Source ISSN

0270-6474

Original Item ID

DOI: 10.1523/JNEUROSCI.1342-09.2010

Abstract

A key in understanding the neurobiology of addiction and developing effective pharmacotherapies is revealing drug-induced plasticity that results in heightened relapse susceptibility. Previous studies have demonstrated that increased extracellular glutamate, but not dopamine, in the nucleus accumbens core (NAcc) is necessary for cocaine-induced reinstatement. In this report, we examined whether drug-induced adaptations that are necessary to generate cocaine-induced reinstatement also determine relapse vulnerability. To do this, rats were assigned to self-administer cocaine under conditions resulting in low (2 h/d; 0.5 mg/kg/infusion, i.v.) or high (6 h/d; 1.0 mg/kg/infusion, i.v.) levels of drug intake since these manipulations produce groups of rats exhibiting differences in the magnitude of cocaine-induced reinstatement. Approximately 19 d after the last session, cocaine-induced drug seeking and extracellular levels of glutamate and dopamine in the NAcc were measured. Contrary to our hypothesis, high-intake rats exhibited a more robust cocaine-induced increase in extracellular levels of dopamine but not glutamate. Further, increased reinstatement in high-intake rats was no longer observed when the D₁ receptor antagonist SCH-23390 was infused into the NAcc. The sensitized dopamine response to cocaine in high-intake rats may involve blunted cystine–glutamate exchange by system x_c⁻. Reduced ¹⁴C-cystine uptake through system x_c⁻ was evident in NAcc tissue slices obtained from high-intake rats, and the augmented dopamine response in these rats was no longer observed when subjects received the cysteine prodrug N-acetyl cysteine. These data reveal a role for drug-induced NAcc dopamine in heightened relapse vulnerability observed in rats with a history of high levels of drug intake.

Comments

Published version. Journal of Neuroscience, Vol. 30, No. 1 (January 2010): 210-217. DOI. © 2010 Society for Neuroscience. Used with permission.

Recommended Citation

Madayag, Aric; Kau, Kristen S.; Lobner, Doug; Mantsch, John R.; Wisniewski, Samantha; and Baker, David A., "Drug-Induced Plasticity Contributing to Heightened Relapse Susceptibility: Neurochemical Changes and Augmented Reinstatement in High-Intake Rats" (2010). Biomedical Sciences Faculty Research and Publications. 106.
https://epublications.marquette.edu/biomedsci_fac/106