Emergence of Endocytosis-Dependent mGlu1 LTD at Nucleus Accumbens Synapses After Withdrawal From Cocaine Self-Administration
Extended-access cocaine self-administration induces a progressive intensification of cue-induced drug craving during withdrawal termed “incubation of cocaine craving”. Rats evaluated after >1 month of withdrawal (when incubation of craving is robust) display alterations in excitatory synapses...
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Synaptic Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnsyn.2018.00036/full |
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| author | Andrew F. Scheyer Andrew F. Scheyer Daniel T. Christian Marina E. Wolf Kuei Y. Tseng |
| author_facet | Andrew F. Scheyer Andrew F. Scheyer Daniel T. Christian Marina E. Wolf Kuei Y. Tseng |
| author_sort | Andrew F. Scheyer |
| collection | DOAJ |
| description | Extended-access cocaine self-administration induces a progressive intensification of cue-induced drug craving during withdrawal termed “incubation of cocaine craving”. Rats evaluated after >1 month of withdrawal (when incubation of craving is robust) display alterations in excitatory synapses onto medium spiny neurons (MSNs) of the nucleus accumbens (NAc), including elevated levels of Ca2+-permeable AMPA receptors (CP-AMPAR) and a transition from group I metabotropic glutamate receptor (mGluR) mGlu5- to mGlu1-mediated synaptic depression. It is important to further characterize the emergent form of mGlu1-mediated synaptic depression because it has been demonstrated that mGlu1 stimulation, by normalizing CP-AMPAR transmission, reduces cue-induced cocaine craving. In the present study, we conducted whole-cell patch-clamp recordings in NAc core MSNs, comparing rats that underwent >35 days of withdrawal from cocaine self-administration to control rats that had self-administered saline. Bath application of the nonselective group I mGluR agonist dihydroxyphenylglycine (DHPG) produced a transient mGlu5-mediated synaptic depression in saline controls, whereas a persistent mGlu1-mediated synaptic depression emerged in cocaine rats. This form of long-term depression (LTD) was abolished by the inclusion of dynamin inhibitory peptide (DIP) in the recording electrode, indicating that it is mediated by removal of CP-AMPARs through a dynamin-dependent endocytosis mechanism. We further showed that CP-AMPAR endocytosis is normally coupled to the PICK1-mediated insertion of Ca2+-impermeable AMPARs (CI-AMPAR). Interestingly, this coupling is not obligatory because disruption of PICK1-mediated CI-AMPAR insertion with pep2-EVKI spared mGlu1-mediated CP-AMPAR endocytosis. Collectively, these results reveal similarities but also differences from mGlu1-LTD observed in other brain regions, and further our understanding of a form of plasticity that may be targeted to reduce cue-induced craving for cocaine and methamphetamine. |
| first_indexed | 2024-04-14T02:37:48Z |
| format | Article |
| id | doaj.art-6c6db9f48a334213864a280ce976dcfa |
| institution | Directory Open Access Journal |
| issn | 1663-3563 |
| language | English |
| last_indexed | 2024-04-14T02:37:48Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Synaptic Neuroscience |
| spelling | doaj.art-6c6db9f48a334213864a280ce976dcfa2022-12-22T02:17:17ZengFrontiers Media S.A.Frontiers in Synaptic Neuroscience1663-35632018-10-011010.3389/fnsyn.2018.00036417152Emergence of Endocytosis-Dependent mGlu1 LTD at Nucleus Accumbens Synapses After Withdrawal From Cocaine Self-AdministrationAndrew F. Scheyer0Andrew F. Scheyer1Daniel T. Christian2Marina E. Wolf3Kuei Y. Tseng4Department of Cellular and Molecular Pharmacology, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesDepartment of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesDepartment of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesDepartment of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesDepartment of Cellular and Molecular Pharmacology, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesExtended-access cocaine self-administration induces a progressive intensification of cue-induced drug craving during withdrawal termed “incubation of cocaine craving”. Rats evaluated after >1 month of withdrawal (when incubation of craving is robust) display alterations in excitatory synapses onto medium spiny neurons (MSNs) of the nucleus accumbens (NAc), including elevated levels of Ca2+-permeable AMPA receptors (CP-AMPAR) and a transition from group I metabotropic glutamate receptor (mGluR) mGlu5- to mGlu1-mediated synaptic depression. It is important to further characterize the emergent form of mGlu1-mediated synaptic depression because it has been demonstrated that mGlu1 stimulation, by normalizing CP-AMPAR transmission, reduces cue-induced cocaine craving. In the present study, we conducted whole-cell patch-clamp recordings in NAc core MSNs, comparing rats that underwent >35 days of withdrawal from cocaine self-administration to control rats that had self-administered saline. Bath application of the nonselective group I mGluR agonist dihydroxyphenylglycine (DHPG) produced a transient mGlu5-mediated synaptic depression in saline controls, whereas a persistent mGlu1-mediated synaptic depression emerged in cocaine rats. This form of long-term depression (LTD) was abolished by the inclusion of dynamin inhibitory peptide (DIP) in the recording electrode, indicating that it is mediated by removal of CP-AMPARs through a dynamin-dependent endocytosis mechanism. We further showed that CP-AMPAR endocytosis is normally coupled to the PICK1-mediated insertion of Ca2+-impermeable AMPARs (CI-AMPAR). Interestingly, this coupling is not obligatory because disruption of PICK1-mediated CI-AMPAR insertion with pep2-EVKI spared mGlu1-mediated CP-AMPAR endocytosis. Collectively, these results reveal similarities but also differences from mGlu1-LTD observed in other brain regions, and further our understanding of a form of plasticity that may be targeted to reduce cue-induced craving for cocaine and methamphetamine.https://www.frontiersin.org/article/10.3389/fnsyn.2018.00036/fullcalcium-permeable AMPA receptorsynaptic transmissioncocaine withdrawallong-term depressionnucleus accumbensmetabotropic glutamate receptor 1 |
| spellingShingle | Andrew F. Scheyer Andrew F. Scheyer Daniel T. Christian Marina E. Wolf Kuei Y. Tseng Emergence of Endocytosis-Dependent mGlu1 LTD at Nucleus Accumbens Synapses After Withdrawal From Cocaine Self-Administration Frontiers in Synaptic Neuroscience calcium-permeable AMPA receptor synaptic transmission cocaine withdrawal long-term depression nucleus accumbens metabotropic glutamate receptor 1 |
| title | Emergence of Endocytosis-Dependent mGlu1 LTD at Nucleus Accumbens Synapses After Withdrawal From Cocaine Self-Administration |
| title_full | Emergence of Endocytosis-Dependent mGlu1 LTD at Nucleus Accumbens Synapses After Withdrawal From Cocaine Self-Administration |
| title_fullStr | Emergence of Endocytosis-Dependent mGlu1 LTD at Nucleus Accumbens Synapses After Withdrawal From Cocaine Self-Administration |
| title_full_unstemmed | Emergence of Endocytosis-Dependent mGlu1 LTD at Nucleus Accumbens Synapses After Withdrawal From Cocaine Self-Administration |
| title_short | Emergence of Endocytosis-Dependent mGlu1 LTD at Nucleus Accumbens Synapses After Withdrawal From Cocaine Self-Administration |
| title_sort | emergence of endocytosis dependent mglu1 ltd at nucleus accumbens synapses after withdrawal from cocaine self administration |
| topic | calcium-permeable AMPA receptor synaptic transmission cocaine withdrawal long-term depression nucleus accumbens metabotropic glutamate receptor 1 |
| url | https://www.frontiersin.org/article/10.3389/fnsyn.2018.00036/full |
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