A Single Brain-Derived Neurotrophic Factor Infusion into the Dorsomedial Prefrontal Cortex Attenuates Cocaine Self-Administration-Induced Phosphorylation of Synapsin in the Nucleus Accumbens during Early Withdrawal
| العنوان: | A Single Brain-Derived Neurotrophic Factor Infusion into the Dorsomedial Prefrontal Cortex Attenuates Cocaine Self-Administration-Induced Phosphorylation of Synapsin in the Nucleus Accumbens during Early Withdrawal |
|---|---|
| المؤلفون: | Wei-Lun Sun, Agnieszka Zelek-Molik, Jacqueline F. McGinty, Sarah A. Eisenstein |
| المصدر: | International Journal of Neuropsychopharmacology |
| بيانات النشر: | Oxford University Press, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, nucleus accumbens, Prefrontal Cortex, Self Administration, Epigenetics of cocaine addiction, Nucleus accumbens, phosphatase, Rats, Sprague-Dawley, chemistry.chemical_compound, Cocaine-Related Disorders, Cocaine, Dopamine Uptake Inhibitors, Neurotrophic factors, Internal medicine, medicine, Animals, Pharmacology (medical), Phosphorylation, Neurotransmitter, Prefrontal cortex, Pharmacology, Brain-derived neurotrophic factor, synapsin, Brain-Derived Neurotrophic Factor, Glutamate receptor, cocaine self-administration, Synapsin, Synapsins, Substance Withdrawal Syndrome, Psychiatry and Mental health, Disease Models, Animal, Endocrinology, chemistry, nervous system, Psychology, Neuroscience, immunoblotting, Research Article, Central Nervous System Agents |
| الوصف: | Background Dysregulation in the prefrontal cortex-nucleus accumbens pathway has been implicated in cocaine addiction. We have previously demonstrated that one intra-dorsomedial prefrontal cortex brain-derived neurotrophic factor (BDNF) infusion immediately following the last cocaine self-administration session caused a long-lasting inhibition of cocaine-seeking and normalized the cocaine-induced disturbance of glutamate transmission in the nucleus accumbens after extinction and a cocaine prime. However, the molecular mechanism mediating the brain-derived neurotrophic factor effect on cocaine-induced alterations in extracellular glutamate levels is unknown. Methods In the present study, we determined the effects of brain-derived neurotrophic factor on cocaine-induced changes in the phosphorylation of synapsin (p-synapsin), a family of presynaptic proteins that mediate synaptic vesicle mobilization, in the nucleus accumbens during early withdrawal. Results Two hours after cocaine self-administration, p-synapsin Ser9 and p-synapsin Ser62/67, but not p-synapsin Ser603, were increased in the nucleus accumbens. At 22 hours, only p-synapsin Ser9 was still elevated. Elevations at both time points were attenuated by an intra-dorsomedial prefrontal cortex brain-derived neurotrophic factor infusion immediately after the end of cocaine self-administration. Brain-derived neurotrophic factor also reduced cocaine self-administration withdrawal-induced phosphorylation of the protein phosphatase 2A C-subunit, suggesting that brain-derived neurotrophic factor disinhibits protein phosphatase 2A C-subunit, consistent with p-synapsin Ser9 dephosphorylation. Further, co-immunoprecipitation demonstrated that protein phosphatase 2A C-subunit and synapsin are associated in a protein-protein complex that was reduced after 2 hours of withdrawal from cocaine self-administration and reversed by brain-derived neurotrophic factor. Conclusions Taken together, these findings demonstrate that brain-derived neurotrophic factor normalizes the cocaine self-administration-induced elevation of p-synapsin in nucleus accumbens that may underlie a disturbance in the probability of neurotransmitter release or represent a compensatory neuroadaptation in response to the hypofunction within the prefrontal cortex-nucleus accumbens pathway during cocaine withdrawal. |
| اللغة: | English |
| تدمد: | 1469-5111 1461-1457 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f2a620d989baeb0c36fb24de8b2e009Test http://europepmc.org/articles/PMC4368877Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8f2a620d989baeb0c36fb24de8b2e009 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14695111 14611457 |
|---|