Cocaine self-administration induces changes in synaptic transmission and plasticity in ventral hippocampus
Autor: | John J. Wagner, Sherri B. Briggs, M. M. Keralapurath |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Pharmacology Medicine (miscellaneous) Hippocampus Long-term potentiation AMPA receptor Neurotransmission gamma-Aminobutyric acid 03 medical and health sciences Psychiatry and Mental health 030104 developmental biology 0302 clinical medicine nervous system Neuroplasticity medicine Excitatory postsynaptic potential GABAergic Psychology Neuroscience 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Addiction Biology. 22:446-456 |
ISSN: | 1355-6215 |
DOI: | 10.1111/adb.12345 |
Popis: | Allowing rats extended access to cocaine self-administration is thought to recapitulate several key aspects of cocaine addiction in humans. Understanding the mechanisms that underlie drug-induced neuroadaptations that persist in the brain after protracted periods of abstinence is crucial towards the goal of developing therapeutic interventions for this disease state. We have employed both whole-cell voltage clamp and extracellular recording technique to assess changes in neurotransmission and long-term potentiation (LTP) in stratum radiatum of the CA1 region using the rat ventral hippocampal slice preparation. Rats allowed to self-administer cocaine daily, including 'long access' (6 hours) sessions, exhibited an increase in the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/N-methyl-d-aspartate current ratio and enhanced excitatory transmission following 3-5 weeks of abstinence. Inhibitory transmission was also significantly decreased in long-access animals, and the AMPA/N-methyl-d-aspartate ratio measured in the absence of GABAergic blockers was greatly enhanced. We also observed a significant reduction of LTP magnitude evoked in the long-access cocaine rats. These findings suggest the presence of synergistic effects of enhanced AMPA and diminished gamma-aminobutyric acid neurotransmission under physiological conditions in the CA1 region of cocaine-taking animals, supporting the conclusion that persisting enhancement of AMPA-mediated transmission and/or inhibition of gamma-aminobutyric acid-mediated transmission promoted a chronic state of potentiation that partially occluded further LTP. This increased output from the ventral hippocampus to other limbic areas would be among the drug-induced neuroadaptations that persist following abstinence from cocaine self-administration and therefore may contribute to the disease state of addiction. |
Databáze: | OpenAIRE |
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