Antinociceptive tolerance to morphine from repeated nociceptive testing in the rat

• Published in: Brain research 2005-06, Vol.1047 (1), p.65-71
• Main Authors: Lane, Diane A., Morgan, Michael M.
• Format: Article
• Language: English
• Subjects: Analgesia; Analgesics, Opioid - pharmacology; Anesthetics, Intravenous - pharmacology; Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Behavioral tolerance; Biological and medical sciences; Dose-Response Relationship, Drug; Drug Tolerance - physiology; Formalin; Fundamental and applied biological sciences. Psychology; Hotplate; Male; Microinjections; Morphine - pharmacology; Neural Pathways - drug effects; Neural Pathways - physiology; Opiates; Pain - drug therapy; Pain - physiopathology; Pain Measurement - drug effects; Pain Threshold - drug effects; Pain Threshold - physiology; Periaqueductal Gray - drug effects; Periaqueductal Gray - physiology; Rats; Rats, Sprague-Dawley; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2005.04.001

Repeated morphine administration has been shown to produce tolerance to the antinociceptive effects of morphine. However, the degree to which repeated morphine administration decreases antinociception is exaggerated by repeated behavioral testing, a phenomenon known as behavioral tolerance. An important question is whether behavioral tolerance can be overcome by direct administration of morphine into the ventrolateral periaqueductal gray (vPAG), a key structure contributing to morphine antinociception. Rats were injected with morphine or saline into the vPAG (Experiment 1) or subcutaneously (Experiment 2) followed 20 min later with hotplate testing. The control groups received the same drug administration, but no nociceptive testing. Repeated nociceptive testing or repeated morphine administration produced antinociceptive tolerance regardless of whether morphine was injected into the vPAG or systemically. Administration of a high dose of morphine (20 mg/kg, s.c.) was able to overcome the development of behavioral tolerance, but not pharmacological tolerance revealing separate mechanisms for these two types of tolerance. These data indicate that behavioral tolerance is independent of the route of morphine administration.