Abstract
A flavor paired with morphine shifted to the right the function relating morphine dose to tail-flick latencies and provoked hyperalgesic responses when rats were tested in the absence of morphine. These learned increases in nociceptive sensitivity were not mediated by alterations in tail-skin temperature. Microinjection of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP-5) into the lateral ventricle reversed the hyperalgesic responses but spared the tolerance to morphine analgesia. By contrast, systemic administration of the noncompetitive NMDA receptor antagonist MK-801 or intrathecal infusion of AP-5 reversed the hyperalgesic responses as well as the tolerance to morphine analgesia. The results demonstrate that associatively mediated tolerance to morphine analgesia can co-occur with hyperalgesic responses and are discussed relative to learned activation of endogenous pronociceptive mechanisms.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Analgesics, Opioid / pharmacology*
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Analysis of Variance
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Animals
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Association Learning / drug effects*
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Association Learning / physiology
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Binding, Competitive / physiology
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Dizocilpine Maleate / pharmacology
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Drinking Behavior / drug effects
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Drug Administration Routes
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Drug Tolerance / physiology*
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Excitatory Amino Acid Antagonists / classification
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Excitatory Amino Acid Antagonists / pharmacology*
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Male
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Morphine / pharmacology*
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Pain Threshold / drug effects*
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Pain Threshold / physiology
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Rats
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Rats, Wistar
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Reaction Time / drug effects
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
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Receptors, N-Methyl-D-Aspartate / physiology
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Regression Analysis
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Taste / physiology
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Thermosensing / drug effects
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Time Factors
Substances
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Analgesics, Opioid
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Excitatory Amino Acid Antagonists
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Receptors, N-Methyl-D-Aspartate
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Dizocilpine Maleate
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2-Amino-5-phosphonovalerate
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Morphine