Effects of systemic, intracerebral, or intrathecal administration of an N-methyl-D-aspartate receptor antagonist on associative morphine analgesic tolerance and hyperalgesia in rats.
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.
McNally
G P
GP
School of Psychology, University of New South Wales, Sydney, Australia.
Westbrook
R F
RF
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000187:drug effects* / Q000502:physiology; D001667:Binding, Competitive / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004327:Drinking Behavior / Q000187:drug effects; D004333:Drug Administration Routes; D004361:Drug Tolerance / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000145:classification / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012044:Regression Analysis; D013649:Taste / Q000502:physiology; D013697:Thermosensing / Q000187:drug effects; D013997:Time Factors
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D009020:Morphine