Lin Lu1, Jamie L Uejima, Sarah M Gray, Jennifer M Bossert, Yavin Shaham. 1. Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland, USA. linlu@bjmu.edu.cn
Abstract
BACKGROUND: We and others reported time-dependent increases in cue-induced cocaine seeking after withdrawal, suggesting that craving incubates over time. Recently, we found that central amygdala extracellular signal-regulated kinases (ERK) and glutamate are involved in this incubation. Here, we further explored the role of central amygdala glutamate in the incubation of cocaine craving by determining the effect of systemic or central amygdala injections of the mGluR2/3 agonist LY379268 (which decreases glutamate release) on cue-induced cocaine seeking during early and late withdrawal. METHODS: Rats were trained to self-administer cocaine for 10 days (6 hours/day); infusions were paired with a tone-light cue. Cocaine seeking and craving after systemic or central amygdala injections of LY379268 were then assessed in extinction tests in the presence of the cocaine-associated cues during early (day 3) or late (day 21) withdrawal. RESULTS: Systemic (1.5 or 3 mg/kg) or central amygdala (.5 or 1.0 microg/side) injections of LY379268 attenuated enhanced extinction responding on day 21 but had no effect on lower extinction responding on day 3. CONCLUSIONS: Results confirm our previous findings on the role of central amygdala glutamate in the incubation of cocaine craving and together with previous reports suggest that mGluR(2/3) agonists should be considered in the treatment of drug relapse.
BACKGROUND: We and others reported time-dependent increases in cue-induced cocaine seeking after withdrawal, suggesting that craving incubates over time. Recently, we found that central amygdala extracellular signal-regulated kinases (ERK) and glutamate are involved in this incubation. Here, we further explored the role of central amygdala glutamate in the incubation of cocaine craving by determining the effect of systemic or central amygdala injections of the mGluR2/3 agonist LY379268 (which decreases glutamate release) on cue-induced cocaine seeking during early and late withdrawal. METHODS:Rats were trained to self-administer cocaine for 10 days (6 hours/day); infusions were paired with a tone-light cue. Cocaine seeking and craving after systemic or central amygdala injections of LY379268 were then assessed in extinction tests in the presence of the cocaine-associated cues during early (day 3) or late (day 21) withdrawal. RESULTS: Systemic (1.5 or 3 mg/kg) or central amygdala (.5 or 1.0 microg/side) injections of LY379268 attenuated enhanced extinction responding on day 21 but had no effect on lower extinction responding on day 3. CONCLUSIONS: Results confirm our previous findings on the role of central amygdala glutamate in the incubation of cocaine craving and together with previous reports suggest that mGluR(2/3) agonists should be considered in the treatment of drug relapse.
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