Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc

Mameli, Manuel; Halbout, Briac; Creton, Cyril; Engblom, David; Parkitna, Jan Rodriguez; Spanagel, Rainer; Lüscher, Christian

doi:10.1038/nn.2367

Cited by 306 publications

(440 citation statements)

References 34 publications

Supporting

Mentioning

412

Contrasting

Unclassified

Order By: Relevance

“…Hence, impaired DA D2/3-mediated neurotransmission within the NAcbS might affect the entire DA cascading circuitry, eventually altering NAcbC activity and consequently behavioral output. Such an influence of the NAcbS over NAcbC functioning in the control of behavior has already been implicated in the context of latent inhibition (Weiner et al, 1999) and neural plasticity (Mameli et al, 2009).…”

Section: Dopamine Receptor Modulation Of Impulsivity M Besson Et Almentioning

confidence: 95%

Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens

Besson

Belin

McNamara

et al. 2009

Neuropsychopharmacol

120

111

View full text Add to dashboard Cite

Previous research has identified the nucleus accumbens (NAcb) as an important brain region underlying inter-individual variation in impulsive behavior. Such variation has been linked to decreased dopamine (DA) D2/3 receptor availability in the ventral striatum of rats exhibiting spontaneously high levels of impulsivity on a 5-choice serial reaction time (5-CSRT) test of sustained visual attention. This study investigated the involvement of DA D2/3 receptors in the NAcb core (NAcbC) and the NAcb shell (NAcbS) in impulsivity. We investigated the effects of a DA D2/3 receptor antagonist (nafadotride) and a DA D2/3 partial agonist (aripiprazole) infused directly into either the NAcbC or NAcbS of rats selected for high (HI) and low (LI) impulsivity on the 5-CSRT task. Nafadotride increased significantly the level of impulsivity when infused into the NAcbS, but decreased impulsivity when infused into the NAcbC of HI rats. By contrast, intraNAcb microinfusions of aripiprazole did not affect impulsivity. Systemic administration of nafadotride had no effect on impulsive behavior but increased the number of omissions and correct response latencies, whereas systemic injections of aripiprazole decreased impulsive and perseverative behavior, and increased the number of omissions and correct response latencies. These findings indicate an opponent modulation of impulsive behavior by DA D2/3 receptors in the NAcbS and NAcbC. Such divergent roles may have relevance for the etiology and treatment of clinical disorders of behavioral control, including attention-deficit hyperactivity disorder and drug addiction.

show abstract

Section: Dopamine Receptor Modulation Of Impulsivity M Besson Et Almentioning

confidence: 95%

Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens

Besson

Belin

McNamara

et al. 2009

Neuropsychopharmacol

120

111

View full text Add to dashboard Cite

show abstract

“…These mice were obtained by crossing C57BL6-Jico wild-type with Pitx3 gfp/gfp mice. These animals have selective GFP expression in dopaminergic neurons in the midbrain, allowing for their accurate identification (Smidt et al, 1997;Zhao et al, 2004;Labouèbe et al, 2007;Mameli et al, 2009;Padgett et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

Morphine Withdrawal Enhances Constitutive μ-Opioid Receptor Activity in the Ventral Tegmental Area

et al. 2012

View full text Add to dashboard Cite

-Opioid receptors (MORs) in the ventral tegmental area (VTA) are pivotally involved in addictive behavior. While MORs are typically activated by opioids, they can also become constitutively active in the absence of any agonist. In the current study, we present evidence that MOR constitutive activity is highly relevant in the mouse VTA, as it regulates GABAergic input to dopamine neurons. Specifically, suppression of MOR constitutive activity with the inverse agonist KC-2-009 enhanced GABAergic neurotransmission onto VTA dopamine neurons. This inverse agonistic effect was fully blocked by the specific MOR neutral antagonist CTOP, which had no effect on GABAergic transmission itself. We next show that withdrawal from chronic morphine further increases the magnitude of inverse agonistic effects at the MOR, suggesting enhanced MOR constitutive activity. We demonstrate that this increase can be an adaptive response to the detrimental elevation in cAMP levels known to occur during morphine withdrawal. These findings offer important insights in the physiological occurrence and function of MOR constitutive activity, and have important implications for therapeutic strategies aimed at normalizing MOR signaling during addiction and opioid overdose.

show abstract

“…Thus, CP-AMPARs, which account for B30% of evoked EPSC amplitude at this withdrawal time, mediate the expression of incubation after prolonged withdrawal (Conrad et al, 2008). CP-AMPARs also accumulate in the mouse NAc after a similar regimen in association with enhanced cocaine craving (Mameli et al, 2009). From the standpoint of synaptic transmission, the presence of CPAMPARs is expected to have important consequences, such as providing a route for Ca 2 þ entry other than NMDARs and thus altering the 'rules' for induction of synaptic plasticity (eg, Mameli et al, 2011).…”

Section: Introductionmentioning

confidence: 95%

Different Adaptations in AMPA Receptor Transmission in the Nucleus Accumbens after Short vs Long Access Cocaine Self-Administration Regimens

Purgianto

Scheyer

Loweth

et al. 2013

Neuropsychopharmacol

View full text Add to dashboard Cite

Ca 2 þ -permeable AMPA receptors (CP-AMPARs) accumulate in the nucleus accumbens (NAc) after B1 month of withdrawal from a long-access cocaine self-administration regimen (6 h/d, 10d). This is functionally significant because CP-AMPARs mediate the 'incubated' cue-induced cocaine craving produced by this regimen. Our present goal was to determine if other commonly employed cocaine selfadministration regimens also elicit CP-AMPAR accumulation. We compared four regimens, named according to whether sessions were short-access (ShA, 2 h) or long-access (LgA, 6 h) and the total number of sessions: LgA/10d (already shown to elicit CP-AMPAR accumulation), ShA/11d, ShA/20-24d, and LgA/20-24d. In the latter regimens, rats began with 10 days of ShA and then entered a differential phase (10-14 days) in which ShA sessions either continued or switched to LgA. Controls self-administered saline. After 440 days of withdrawal, whole-cell patch-clamp recordings were performed in NAc core medium spiny neurons to assess the contribution of CP-AMPAR transmission, based on the magnitude of synaptic suppression elicited by bath application of the selective CP-AMPAR antagonist naspm (100 mM). Naspm produced a non-significant (B10%) attenuation of electrically evoked local excitatory postsynaptic current in the saline and ShA groups. By contrast, a significant naspm-induced synaptic attenuation (25-30%) was observed in both the LgA groups. Further analyses indicate that this emergence of CP-AMPAR transmission in the LgA groups is associated with increased baseline responsiveness of MSN to excitatory drive. Together with data on cocaine infusions in each group, our results show that CP-AMPAR accumulation and enhanced glutamate transmission is associated with longer sessions (6 h), rather than the number of sessions or cocaine infusions.

show abstract

Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc

Cited by 306 publications

References 34 publications

Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens

Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens

Morphine Withdrawal Enhances Constitutive μ-Opioid Receptor Activity in the Ventral Tegmental Area

Different Adaptations in AMPA Receptor Transmission in the Nucleus Accumbens after Short vs Long Access Cocaine Self-Administration Regimens

Contact Info

Product

Resources

About