Nucleus Accumbens Long-Term Depression and the Expression of Behavioral Sensitization

Brebner, Karen; Wong, Tak Pan; Liu, Lidong; Liu, Yitao; Campsall, Paul A.; Gray, Sarah L.; Phelps, Lindsay; Phillips, Anthony G.; Wang, Yu Tian

doi:10.1126/science.1116894

Cited by 269 publications

(328 citation statements)

References 28 publications

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“…In the same aforementioned study, Ahmadian et al (2004) demonstrated that induction of LTD in hippocampal CA1 slices is associated with increased GluR2 tyrosine phosphorylation, and is prevented by postsynaptic application of the GluR2 3Y peptide. Likewise Brebner et al (2005) demonstrate that Tat-GluR2 3Y blocks the induction of LTD in nucleus accumbens neurons in an in vitro slice preparation. This is consistent with other studies that have implied a role for AMPA receptor endocytosis in mediating LTD (Wang and Linden, 2000;Xia et al, 2000).…”

Section: Blockade Of Ampa Receptor Endocytosis Does Not Effect the Acmentioning

confidence: 64%

“…at a dose of 6 mg/kg 30 min before testing. Dose and route of administration for Tat-GluR2 3Y and Tat-GluR2 3S were chosen with reference to Brebner et al (2005). Dose and route of administration of Ro 25-6981 was chosen with reference to Fox et al (2006).…”

Section: Drugsmentioning

confidence: 99%

“…Dose and route of administration of Ro 25-6981 was chosen with reference to Fox et al (2006). Previous studies from our laboratory (Brebner et al, 2005) have shown that the same dose (1.5 mmol/kg) of fluorescently tagged Tat-GluR2 3Y reaches peak concentrations in the brain 90 min after an i.v. infusion with a single exponential decay with a half-life of 4 h. Accordingly, concentrations of the Tat-GluR2 3Y peptide would reach undetectable levels in the brain by 24 h postinjection.…”

Section: Drugsmentioning

confidence: 99%

“…When delivered into postsynaptic neurons, a synthetic peptide containing this sequence of amino acids (GluR2 3Y ) blocks LTD by interfering with the facilitated endocytosis of AMPA receptors, the last step of LTD expression, without affecting any upstream signaling steps (Ahmadian et al, 2004;Brebner et al, 2005). The peptide is fused to the cell membrane transduction domain of the HIV-1 protein (Schwarze et al, 1999) making a TatGluR2 3Y peptide, rendering it membrane permeable and capable of exerting its physiological effects following systemic administration (Brebner et al, 2005).…”

Section: Blockade Of Ampa Receptor Endocytosis Does Not Effect the Acmentioning

confidence: 99%

“…It follows that disruption of AMPA receptor endocytosis (which selectively blocks the formation of LTD) may exert a selective effect on the extinction of a previously established fear memory, without affecting the acquisition of learned fear itself (formation of a new memory). To test this hypothesis directly, we employed the use of the Tat-GluR2 3Y peptide, which we have shown previously to block the GluR2-dependent, regulated AMPA receptor endocytosis associated with the formation of LTD in structures such as the nucleus accumbens and dorsal hippocampus (Brebner et al, 2005;Fox et al, 2007;Wong et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Disruption of AMPA Receptor Endocytosis Impairs the Extinction, but not Acquisition of Learned Fear

Dalton

Wang

Floresco

et al. 2007

Neuropsychopharmacol

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135

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Synaptic plasticity in the form of long-term potentiation (LTP) plays a critical role in the formation of a Pavlovian fear association. However, the role that synaptic plasticity plays in the suppression of a learned fear response remains to be clarified. Here, we assessed the role that long-term depression (LTD) plays in the acquisition, expression, and extinction of a conditioned fear response. We report that blockade of LTD with a GluR2-derived peptide (Tat-GluR2 3Y ; 1.5 mmol/kg, i.v.) that blocks regulated a-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor endocytosis during an initial extinction training session disrupted both the expression and recall of extinction learning. A similar impairment of extinction during training, but not recall, was observed when NMDA receptor-dependent LTD was inhibited through the selective blockade of NMDA NR2B receptors with Ro 25-6981. In contrast, blockade of LTD with Tat-GluR2 3Y during fear conditioning or during a fear recall test did not effect the expression or recall of either contextual or cue-induced conditioned fear. Similarly, administration of Tat-GluR2 3Y prior to an extinction recall test did not affect spontaneous recovery or rate of re-extinction in previously extinguished rats. These data demonstrate that AMPA receptor endocytosis does not mediate acquisition or expression of conditioned fear, but may play a role in the extinction of fear memories. Furthermore, these findings suggest that LTD may be a molecular mechanism that facilitates the selective modification of a learned association while leaving intact the ability to form a new memory.

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Section: Blockade Of Ampa Receptor Endocytosis Does Not Effect the Acmentioning

confidence: 64%

Section: Drugsmentioning

confidence: 99%

Section: Drugsmentioning

confidence: 99%

Section: Blockade Of Ampa Receptor Endocytosis Does Not Effect the Acmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Disruption of AMPA Receptor Endocytosis Impairs the Extinction, but not Acquisition of Learned Fear

Dalton

Wang

Floresco

et al. 2007

Neuropsychopharmacol

Self Cite

144

135

View full text Add to dashboard Cite

show abstract

Opioid withdrawal for 4 days prevents synaptic depression induced by low dose of morphine or naloxone in rat hippocampal CA1 area in vivo

Dong¹,

Han

Cao

et al. 2009

Hippocampus

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The formation of memory is believed to depend on experience- or activity-dependent synaptic plasticity, which is exquisitely sensitive to psychological stress since inescapable stress impairs long-term potentiation (LTP) but facilitates long-term depression (LTD). Our recent studies demonstrated that 4 days of opioid withdrawal enables maximal extents of both hippocampal LTP and drug-reinforced behavior; while elevated-platform stress enables these phenomena at 18 h of opioid withdrawal. Here, we examined the effects of low dose of morphine (0.5 mg kg(-1), i.p.) or the opioid receptor antagonist naloxone (1 mg kg(-1), i.p.) on synaptic efficacy in the hippocampal CA1 region of anesthetized rats. A form of synaptic depression was induced by low dose of morphine or naloxone in rats after 18 h but not 4 days of opioid withdrawal. This synaptic depression was dependent on both N-methyl-D-aspartate receptor and synaptic activity, similar to the hippocampal long-term depression induced by low frequency stimulation. Elevated-platform stress given 2 h before experiment prevented the synaptic depression at 18 h of opioid withdrawal; in contrast, the glucocorticoid receptor (GR) antagonist RU38486 treatment (20 mg kg(-1), s.c., twice per day for first 3 days of withdrawal), or a high dose of morphine reexposure (15 mg kg(-1), s.c., 12 h before experiment), enabled the synaptic depression on 4 days of opioid withdrawal. This temporal shift of synaptic depression by stress or GR blockade supplements our previous findings of potentially correlated temporal shifts of LTP induction and drug-reinforced behavior during opioid withdrawal. Our results therefore support the idea that stress experience during opioid withdrawal may modify hippocampal synaptic plasticity and play important roles in drug-associated memory. (c) 2009 Wiley-Liss, Inc.

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Potentiation of synaptic strength and intrinsic excitability in the nucleus accumbens after 10 days of morphine withdrawal

Shi

Wei

et al. 2012

J of Neuroscience Research

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Neuroadaptations in the nucleus accumbens (NAc) are associated with the development of drug addiction. Plasticity in synaptic strength and intrinsic excitability of NAc medium spiny neurons (MSNs) play critical roles in addiction induced by different classes of abused drugs. However, it is unknown whether morphine exposure influences synaptic strength, intrinsic excitability or both in NAc. Here we show that chronic withdrawal (10 days after the last injection) from repeated morphine exposure elicited potentiation in both glutamatergic synaptic strength and intrinsic excitability of MSNs in NAc shell (NAcSh). The potentiation of synaptic strength was demonstrated by an increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs), a decrease in the paired-pulse ratio (PPR), and an increase in the ratio of α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR)- to N-methyl-D-aspartate receptors (NMDAR)-mediated currents. The potentiation of intrinsic excitability was mediated by inhibition of the sustained potassium currents via extrasynaptic NMDAR activation. The function of the presynaptic group II metabotropic glutamate receptors (mGluR2/3) was downregulated, enhancing the probability of glutamate release on synaptic terminals during chronic morphine withdrawal. Pretreatment with the mGluR2/3 agonist LY379268 completely blocked potentiation of both synaptic strength and intrinsic excitability. These results suggest that chronic morphine withdrawal downregulates mGluR2/3 to induce potentiation of MSN glutamatergic synapse via increased glutamate release, leading to potentiation of intrinsic excitability. Such potentiation of both synaptic strength and intrinsic excitability might contribute to neuroadaptations induced by morphine application.

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Nucleus Accumbens Long-Term Depression and the Expression of Behavioral Sensitization

Cited by 269 publications

References 28 publications

Disruption of AMPA Receptor Endocytosis Impairs the Extinction, but not Acquisition of Learned Fear

Disruption of AMPA Receptor Endocytosis Impairs the Extinction, but not Acquisition of Learned Fear

Opioid withdrawal for 4 days prevents synaptic depression induced by low dose of morphine or naloxone in rat hippocampal CA1 area in vivo

Potentiation of synaptic strength and intrinsic excitability in the nucleus accumbens after 10 days of morphine withdrawal

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