Archival ReportA Shift in the Role of Glutamatergic Signaling in the Nucleus Accumbens Core With the Development of an Addicted Phenotype
Section snippets
Subjects
Adult male (n = 38) and female (n = 48) Sprague-Dawley rats were used in this study. Both male and female rats were included to increase the power of detecting a shift in the mechanisms of cocaine reinforcement by stage of addiction. Importantly, we recently showed that motivation for cocaine, measured following the same short-access and extended-access conditions used here, does not differ between male and female rats [(38); also, see Figure 1]. To facilitate rapid acquisition of cocaine
Effect of Short-Access Versus Extended-Access Cocaine Self-Administration on Subsequent Motivation for Cocaine and Cocaine Seeking
During the 10 days of cocaine self-administration under the extended-access discrete trials procedure, rats self-administered a high level of cocaine (average number of infusions was 68.9 ± 2.0 versus the set 20 infusions/day limit in the short-access group), and as expected, female rats self-administered a greater number of infusions than did male rats (71.8 ± 2.0 versus 64.2 ± 4.3, respectively; t11 = 4.2, p < .05). As expected, extended-access rats maintained a markedly higher level of PR
Discussion
The goal of this study was to examine the role of glutamatergic receptor signaling in the NAc in the motivation for cocaine using conditions known to produce an addicted versus a nonaddicted phenotype. As expected, rats in the extended-access group showed a markedly higher level of motivation for cocaine, as well as higher levels of cocaine seeking under both extinction and reinstatement conditions, following abstinence as compared with short-access control rats, thus confirming the development
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2018, Pharmacology Biochemistry and BehaviorCitation Excerpt :Thus far, the results obtained from studies using the progressive ratio schedule and the threshold procedure have revealed similar findings. For example, both procedures have shown differential effects of short versus extended access self-administration on motivation for cocaine (Doyle et al., 2014; Kawa et al., 2016; Ramôa et al., 2013, 2014; Zimmer et al., 2012). Following short access self-administration, motivation for the drug is stable and does not increase over time or following abstinence (Doyle et al., 2014; Ramôa et al., 2013, 2014; Roberts et al., 2007).
One month of cocaine abstinence potentiates rapid dopamine signaling in the nucleus accumbens core
2016, NeuropharmacologyCitation Excerpt :DA dampens the effect of glutamatergic input from the PFC, and this inhibitory action appears to be mediated through D2 receptors (Brady and O'Donnell, 2004; Goto and Grace, 2005). Following abstinence, these two neurotransmitters may thus exert opposing actions on behavior, with glutamate potentiating drug-seeking and DA blunting this effect (Doyle et al., 2014; Ramôa et al., 2014). Future experiments could investigate the link between glutamate and abstinence-induced alterations in dopamine signaling, for example, by employing voltammetry and targeted inotophoretic delivery of agonists and antagonists (Owesson-White et al., 2016).
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