Role of the Major Glutamate Transporter GLT1 in Nucleus Accumbens Core Versus Shell in Cue-Induced Cocaine-Seeking Behavior
| Autor: | Kathryn D. Fischer, Alexander C.W. Houston, George V. Rebec |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Kainic acid Blotting Western Pharmacology Nucleus accumbens Nucleus Accumbens Article Rats Sprague-Dawley Cocaine-Related Disorders chemistry.chemical_compound Downregulation and upregulation Recurrence medicine Animals Dihydrokainic acid Analysis of Variance Aspartic Acid Kainic Acid Behavior Animal General Neuroscience Ceftriaxone Glutamate receptor Transporter Feeding Behavior Rats Substance Withdrawal Syndrome Blockade Excitatory Amino Acid Transporter 2 chemistry Conditioning Operant Cues medicine.drug |
| Zdroj: | The Journal of Neuroscience. 33:9319-9327 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.3278-12.2013 |
| Popis: | Relapse to cocaine-seeking behavior requires an increase in nucleus accumbens (NAc) core glutamate transmission. Decreased expression of glutamate type I transporter (GLT1), which is responsible for >90% of glutamate clearance, occurs in the core of rats withdrawn from cocaine self-administration, while treatment with ceftriaxone, a β-lactam antibiotic previously shown to increase GLT1 expression and function in rodents, upregulates GLT1 and attenuates cue-induced cocaine reinstatement. Here, we tested the effects of increasing GLT1 expression on cue-induced cocaine seeking in rats exposed to either limited (2 h/d) or extended (6 h/d) cocaine access followed by short (2 d) or long (45 d) withdrawal periods. Treatment with ceftriaxone (200 mg/kg, i.p.) upregulated core GLT1 expression and attenuated cue-induced cocaine-seeking behavior only in rats exposed to long withdrawal periods, with a greater effect in the extended-access condition. Pearson's correlation revealed GLT1 expression in core to be inversely correlated with cue-induced cocaine-seeking behavior. To localize the effects of GLT1 upregulation within NAc, we tested the hypothesis that blockade of GLT1 in NAc core, but not shell, would reverse the ceftriaxone-mediated effect. Rats withdrawn from cocaine self-administration were treated with the same dose of ceftriaxone followed by intracore or intrashell infusions of one of two GLT1 blockers, dihydrokainic acid (500 μm) ordl-threo-β-benzyloxyaspartate (250 μm), or saline. Our results reveal that the ceftriaxone-mediated attenuation of cue-induced cocaine reinstatement is reversed by GLT1 blockade in core, but not shell, and further implicate core GLT1 as a potential therapeutic target for cocaine relapse. |
| Databáze: | OpenAIRE |
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