Neuroadaptations in the Dentate Gyrus Following Contextual Cued Reinstatement of Methamphetamine Seeking
Autor: | Noah L Steiner, Sucharita S. Somkuwar, McKenzie J. Fannon, Alice E. Zemljic-Harpf, Brian P. Head, Chitra D. Mandyam, Melissa H. Galinato, Michelle An, Yoshio Takashima |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Histology Drug-Seeking Behavior Hippocampus Glutamic Acid Self Administration Neurotransmission Hippocampal formation Article Extinction Psychological Methamphetamine 03 medical and health sciences Glutamatergic 0302 clinical medicine medicine Animals Rats Wistar Neurons Chemistry General Neuroscience Dentate gyrus Calcium-Binding Proteins Microfilament Proteins Excitatory Postsynaptic Potentials Granule cell Receptors GABA-A Rats 030104 developmental biology medicine.anatomical_structure Oncogene Proteins v-fos Gene Expression Regulation Dentate Gyrus Excitatory postsynaptic potential Conditioning Operant Central Nervous System Stimulants Microglia Anatomy Cues Neuroscience 030217 neurology & neurosurgery medicine.drug |
Popis: | Abstinence from unregulated methamphetamine self-administration increases hippocampal dependent, context-driven reinstatement of methamphetamine seeking. The current study tested the hypothesis that alterations in the functional properties of granule cell neurons (GCNs) in the dentate gyrus (DG) of the hippocampus in concert with altered expression of synaptic plasticity-related proteins and ultrastructural changes in the DG are associated with enhanced context-driven methamphetamine-seeking behavior. Whole-cell patch-clamp recordings were performed in acute brain slices from methamphetamine naïve (controls) and methamphetamine experienced animals (during acute withdrawal, during abstinence, after extinction and after reinstatement). Spontaneous excitatory postsynaptic currents (sEPSCs) and intrinsic excitability were recorded from GCNs. Reinstatement of methamphetamine seeking increased sEPSC frequency and produced larger amplitude responses in GCNs compared to controls and all other groups. Reinstatement of methamphetamine seeking reduced spiking capability in GCNs compared to controls, and all other groups, as indicated by reduced intrinsic spiking elicited by increasing current injections, membrane resistance and fast afterhyperpolarization. In rats that reinstated methamphetamine seeking, these altered electrophysiological properties of GCNs were associated with enhanced expression of Fos, GluN2A subunits and PSD95 and reduced expression of GABA(A) subunits in the DG and enhanced expression of synaptic PSD in the molecular layer. The alterations in functional properties of GCNs and plasticity related proteins in the DG paralleled with no changes in structure of microglial cells in the DG. Taken together, our results demonstrate that enhanced reinstatement of methamphetamine seeking results in alterations in intrinsic spiking and spontaneous glutamatergic synaptic transmission in the GCNs and concomitant increases in neuronal activation of GCNs, and expression of GluNs and decreases in GABA(A) subunits that may contribute to the altered synaptic connectivity – neuronal circuitry – and activity in the hippocampus, and enhance propensity for relapse. |
Databáze: | OpenAIRE |
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