Abstract
In order to further characterize the actions of cocaine on synaptic activity in the hippocampus, recordings of field excitatory postsynaptic potentials in the CA1 region of the rat hippocampal slice preparation were used to monitor drug effects on long-term potentiation (LTP) evoked in response to stimulation of the Schaffer collateral pathway. Cocaine had dose-dependent, biphasic effects on the magnitude of LTP at these excitatory synapses in the stratum radiatum ranging from a significant enhancement of LTP at intermediate drug concentrations (5-10 microM), to an inhibition of LTP at a relatively high drug concentration (30 microM). The local anesthetic lidocaine had only inhibitory effects on the induction of LTP at all concentrations examined (10-75 microM), whereas the monoamine transporter antagonists, WIN 35348 (1 microM) or GBR 12935 (5 microM) significantly enhanced the magnitude of LTP. The D(2)-like dopamine receptor antagonist, eticlopride was effective in preventing this action of cocaine, whereas pretreatment with the D(1/5) antagonist, SCH 23390 was ineffective. These results suggest that endogenously released dopamine, in the presence of cocaine (5-10 microM), can act via D(2)-like receptors to significantly increase the magnitude of LTP in the CA1 region of the hippocampus.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenergic beta-Antagonists / pharmacology
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Anesthetics, Local / pharmacology
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Animals
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Benzazepines / pharmacology
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Cocaine / analogs & derivatives
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Cocaine / pharmacology*
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Desipramine / pharmacology
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Dopamine Antagonists / pharmacology
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Dopamine Uptake Inhibitors / pharmacology*
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Dose-Response Relationship, Drug
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Drug Interactions
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Electric Stimulation / methods
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Enzyme Inhibitors / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Excitatory Postsynaptic Potentials / radiation effects
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Fluoxetine / analogs & derivatives
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Fluoxetine / pharmacology
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Hippocampus / drug effects*
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Hippocampus / physiology
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Hippocampus / radiation effects
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In Vitro Techniques
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Lidocaine / pharmacology
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Long-Term Potentiation / drug effects*
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Long-Term Potentiation / physiology
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Neurotransmitter Uptake Inhibitors / pharmacology
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Piperazines / pharmacology
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Propranolol / pharmacology
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Rats
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Rats, Sprague-Dawley
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Salicylamides / pharmacology
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Tetrodotoxin / pharmacology
Substances
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Adrenergic beta-Antagonists
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Anesthetics, Local
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Benzazepines
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Dopamine Antagonists
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Dopamine Uptake Inhibitors
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Enzyme Inhibitors
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Neurotransmitter Uptake Inhibitors
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Piperazines
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Salicylamides
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Fluoxetine
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nisoxetine
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Tetrodotoxin
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Lidocaine
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1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine
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Propranolol
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Cocaine
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eticlopride
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Desipramine