Acute and Chronic Dopamine Receptor Stimulation Modulates AMPA Receptor Trafficking in Nucleus Accumbens Neurons Cocultured with Prefrontal Cortex Neurons

Sun, Xiu; Milovanovic, Michael; Zhao, Yun; Wolf, Marina E.

doi:10.1523/jneurosci.0258-08.2008

Cited by 100 publications

(161 citation statements)

References 101 publications

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“…The magnitude of these effects was similar to previous studies (Barak et al, 2013;Neasta et al, 2010). These findings are interesting given that dopamine D1-like agonists increase AMPAR insertion into NAC MSNs through a process involving CAMKIIa (Anderson et al, 2008;Sun et al, 2008) and that both dopamine and CAMKIIa have been shown to be important for the expression of psychostimulant sensitization and drugseeking behavior (Licata and Pierce, 2003;Loweth et al, 2008;Pierce et al, 1998). In fact, lentiviral-mediated knockdown of CAMKIIa in the NACsh reduced motivation to self-administer cocaine on a PR schedule (Wang et al, 2010a).…”

Section: Intra-cerebroventricular Mtorc1 Inhibition Reduces Pr Responsupporting

confidence: 86%

mTORC1 Inhibition in the Nucleus Accumbens ‘Protects’ Against the Expression of Drug Seeking and ‘Relapse’ and Is Associated with Reductions in GluA1 AMPAR and CAMKIIα Levels

James

Quinn

Ong

et al. 2014

Neuropsychopharmacol

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The mechanistic target of rapamycin complex 1 (mTORC1) is necessary for synaptic plasticity, as it is critically involved in the translation of synaptic transmission-related proteins, such as Ca 2 þ /Calmodulin-dependent kinase II alpha (CAMKIIa) and AMPA receptor subunits (GluAs). Although recent studies have implicated mTORC1 signaling in drug-motivated behavior, the ineffectiveness of rapamycin, an mTORC1 inhibitor, in suppressing cocaine self-administration has raised questions regarding the specific role of mTORC1 in drug-related behaviors. Here, we examined mTORC1's role in three drug-related behaviors: cocaine taking, withdrawal, and reinstatement of cocaine seeking, by measuring indices of mTORC1 activity and assessing the effect of intra-cerebroventricular rapamycin on these behaviors in rats. We found that withdrawal from cocaine self-administration increased indices of mTORC1 activity in the nucleus accumbens (NAC). Intra-cerebroventricular rapamycin attenuated progressive ratio (PR) break points and reduced phospho-p70 ribosomal S6 kinase, GluA1 AMPAR, and CAMKIIa levels in the NAC shell (NACsh) and core (NACc). In a subsequent study, we treated rats with intra-NACsh infusions of rapamycin (2.5 mg/side/day for 5 days) during cocaine self-administration and then tracked the expression of addiction-relevant behaviors through to withdrawal and extinction. Rapamycin reduced drug seeking in signaled non-drug-available periods, PR responding, and cue-induced reinstatement, with these effects linked to reduced mTORC1 activity, total CAMKIIa, and GluA1 AMPAR levels in the NACsh. Together, these data highlight a role for mTORC1 in the neural processes that control the expression and maintenance of drug reward, including protracted relapse vulnerability. These effects appear to involve a role for mTORC1 in the regulation of GluA1 AMPARs and CAMKIIa in the NACsh.

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Section: Intra-cerebroventricular Mtorc1 Inhibition Reduces Pr Responsupporting

confidence: 86%

mTORC1 Inhibition in the Nucleus Accumbens ‘Protects’ Against the Expression of Drug Seeking and ‘Relapse’ and Is Associated with Reductions in GluA1 AMPAR and CAMKIIα Levels

James

Quinn

Ong

et al. 2014

Neuropsychopharmacol

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“…Interestingly, following repeated amphetamine treatment, amphetamine-induced increases in extracellular DA appear to be enhanced in shell, but not core (Giorgi et al, 2005;Pierce and Kalivas, 1995). As increased DA receptor signaling can promote AMPAR trafficking to synapses in NAc MSNs (Sun et al, 2008), it remains to be determined whether changes in the DA-enhancing properties of amphetamine in core vs shell might explain the regionselective AMPAR plasticity effects of acute vs repeated amphetamine.…”

Section: Nac Subregion-specific Effects Of Amphetamine On Synaptic Ammentioning

confidence: 99%

“…In terms of our current study, the resulting increase in dopaminergic signaling is very likely a significant contributor to the induction of drug-induced depotentiation in the NAc shell. For example, while DA D1 receptor activation has been shown to promote the delivery of AMPARs to the surface of NAc MSNs (Chao et al, 2002), after repeated bouts of DA exposure, this effect of D1R activation is lost (Sun et al, 2008). Furthermore, a recent study found that prolonged ex vivo D1 receptor activation, while having no effect on AMPARs in NAc shell MSNs during the first several days of abstinence from cocaine self-administration, reduced the AMPAR/NMDAR if delivered following several weeks of abstinence (Ortinski et al, 2012).…”

Section: Mechanisms Underlying Synaptic Depotentiationmentioning

confidence: 99%

Cocaine and Amphetamine Induce Overlapping but Distinct Patterns of AMPAR Plasticity in Nucleus Accumbens Medium Spiny Neurons

Jedynak

Hearing

Ingebretson

et al. 2015

Neuropsychopharmacol

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Repeated exposure to psychostimulant drugs such as cocaine or amphetamine can promote drug-seeking and -taking behavior. In rodent addiction models, persistent changes in excitatory glutamatergic neurotransmission in the nucleus accumbens (NAc) appear to drive this drug-induced behavioral plasticity. To study whether changes in glutamatergic signaling are shared between or exclusive to specific psychostimulant drugs, we examined synaptic transmission from mice following repeated amphetamine or cocaine administration. Synaptic transmission mediated by AMPA-type glutamate receptors was potentiated in the NAc shell 10-14 days following repeated amphetamine or cocaine treatment. This synaptic enhancement was depotentiated by re-exposure to amphetamine or cocaine. By contrast, in the NAc core only repeated cocaine exposure enhanced synaptic transmission, which was subsequently depotentiated by an additional cocaine but not amphetamine injection during drug abstinence. To better understand the drug-induced depotentiation, we replicated these in vivo findings using an ex vivo model termed 'challenge in the bath,' and showed that drug-induced decreases in synaptic strength occur rapidly (within 30 min) and require activation of metabotropic glutamate receptor 5 (mGluR5) and protein synthesis in the NAc shell, but not NAc core. Overall, these data demonstrate the specificity of neuronal circuit changes induced by amphetamine, introduce a novel method for studying drug challenge-induced plasticity, and define NAc shell medium spiny neurons as a primary site of persistent AMPA-type glutamate receptor plasticity by two widely used psychostimulant drugs.

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“…Elevated levels of ERK1/2 phosphorylation are observed in corticolimbic areas after cocaine administration (Valjent et al, 2000). Moreover, short-term cocaine potentiates synaptic responses in ventral tegmental area dopamine neurons by promoting the rapid insertion of surface glutamate receptors (Borgland et al, 2004;Sun et al, 2008;Ferrario et al, 2011). ERK1/2 activation is also observed after amphetamine injections (Choe et al, 2002), and this requires both D1Rs and NMDARs (Valjent et al, 2005).…”

Section: G Drugs Of Abusementioning

confidence: 99%

Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders

Goebel-Goody

Baum²,

Paspalas³

et al. 2011

Pharmacol Rev

145

166

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Acute and Chronic Dopamine Receptor Stimulation Modulates AMPA Receptor Trafficking in Nucleus Accumbens Neurons Cocultured with Prefrontal Cortex Neurons

Cited by 100 publications

References 101 publications

mTORC1 Inhibition in the Nucleus Accumbens ‘Protects’ Against the Expression of Drug Seeking and ‘Relapse’ and Is Associated with Reductions in GluA1 AMPAR and CAMKIIα Levels

mTORC1 Inhibition in the Nucleus Accumbens ‘Protects’ Against the Expression of Drug Seeking and ‘Relapse’ and Is Associated with Reductions in GluA1 AMPAR and CAMKIIα Levels

Cocaine and Amphetamine Induce Overlapping but Distinct Patterns of AMPAR Plasticity in Nucleus Accumbens Medium Spiny Neurons

Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders

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