title: Cocaine self-administration induces changes in synaptic transmission and plasticity in ventral hippocampus.
abstract: 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.
authors.affiliation: Department of Physiology & Pharmacology, The University of Georgia, Athens, GA, USA.|Interdisciplinary Toxicology Program, University of Georgia, Athens, GA, USA.
authors.forename: Madhusudhanan M
authors.initials: MM
authors.lastname: Keralapurath
authors.affiliation: Department of Physiology & Pharmacology, The University of Georgia, Athens, GA, USA.|Neuroscience Program, University of Georgia, Athens, GA, USA.
authors.forename: Sherri B
authors.initials: SB
authors.lastname: Briggs
authors.affiliation: Department of Physiology & Pharmacology, The University of Georgia, Athens, GA, USA.|Interdisciplinary Toxicology Program, University of Georgia, Athens, GA, USA.|Neuroscience Program, University of Georgia, Athens, GA, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Wagner
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders; D003216:Conditioning, Operant; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D009435:Synaptic Transmission / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
chemical_list: D018765:Dopamine Uptake Inhibitors; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D003042:Cocaine
keywords: EPSC; IPSC; cocaine self-administration; ex vivo slice; rat; ventral hippocampus