GluN2B-Containing NMDA Receptors Blockade Rescues Bidirectional Synaptic Plasticity in the Bed Nucleus of the Stria Terminalis of Cocaine Self-Administering Rats
| Autor: | Catherine P Normandeau, Andrea A. Jones, Cynthia Di Prospero, Eric Dumont, Julian deBacker, Elysia Mechefske, Scott J. Hayton, Emily R. Hawken, James Gardner Gregory |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Patch-Clamp Techniques Drug-Seeking Behavior Self Administration AMPA receptor Receptors N-Methyl-D-Aspartate Tissue Culture Techniques Cocaine-Related Disorders Random Allocation Cocaine Dopamine Uptake Inhibitors Dietary Sucrose Neuroplasticity Animals Medicine Rats Long-Evans Receptors AMPA Long-term depression Pharmacology Neuronal Plasticity business.industry Excitatory Postsynaptic Potentials Long-term potentiation Substance Withdrawal Syndrome Psychiatry and Mental health Stria terminalis Synapses Synaptic plasticity Excitatory postsynaptic potential NMDA receptor Original Article Septal Nuclei business Neuroscience |
| Zdroj: | Neuropsychopharmacology. 40:394-405 |
| ISSN: | 1740-634X 0893-133X |
| DOI: | 10.1038/npp.2014.182 |
| Popis: | Drugs of abuse have detrimental effects on homeostatic synaptic plasticity in the motivational brain network. Bidirectional plasticity at excitatory synapses helps keep neural circuits within a functional range to allow for behavioral flexibility. Therefore, impaired bidirectional plasticity of excitatory synapses may contribute to the behavioral hallmarks of addiction, yet this relationship remains unclear. Here we tracked excitatory synaptic strength in the oval bed nucleus of the stria terminalis (ovBNST) using whole-cell voltage-clamp recordings in brain slices from rats self-administering sucrose or cocaine. In the cocaine group, we measured both a persistent increase in AMPA to NMDA ratio (A:N) and slow decay time of NMDA currents throughout the self-administration period and after withdrawal from cocaine. In contrast, the sucrose group exhibited an early increase in A:N ratios (acquisition) that returned toward baseline values with continued self-administration (maintenance) and after withdrawal. The sucrose rats also displayed a decrease in NMDA current decay time with continued self-administration (maintenance), which normalized after withdrawal. Cocaine self-administering rats exhibited impairment in NMDA-dependent long-term depression (LTD) that could be rescued by GluN2B-containing NMDA receptor blockade. Sucrose self-administering rats demonstrated no impairment in NMDA-dependent LTD. During the maintenance period of self-administration, in vivo (daily intraperitoneally for 5 days) pharmacologic blockade of GluN2B-containing NMDA receptors did not reduce lever pressing for cocaine. However, in vivo GluN2B blockade did normalize A:N ratios in cocaine self-administrating rats, and dissociated the magnitude of ovBNST A:N ratios from drug-seeking behavior after protracted withdrawal. Altogether, our data demonstrate when and how bidirectional plasticity at ovBNST excitatory synapses becomes dysfunctional with cocaine self-administration and that NMDA-mediated potentiation of AMPA receptors in this region may be part of the neural circuits of drug relapse. |
| Databáze: | OpenAIRE |
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