Single-dose tolerance to antinociception, and physical dependence on beta-endorphin in mice.
beta-Endorphin (B-EN) injected intracerebroventricularly in mice produced a rapid onset, dose-dependent antinociceptive effect. The median analgesic dose (AD50) 30 min following administration was found to be 270 ng/mouse (3.7 nmoles/kg). B-EN produced an acute, single-dose tolerance which was characterized by its dose dependence and the time course of its development. Single-dose tolerance development was demonstrable with doses twice or more the AD50. Tolerance was maximal at about 12 h following the priming dose and disappeared within 48 h. Tolerance was accompanied by some degree of physical dependence as noted by signs of naloxone-precipitated withdrawal similar to those elicitable in the morphine-dependent state. Tolerance development to B-EN was blocked by the simultaneous administration of naloxone and also by pretreatment with 0.35 mg/kg actinomycin D or 30 mg/kg cycloheximide 30 min before B-EN. It appears that single-dose tolerance to B-EN was initiated by processes similar to those involved with tolerance resulting from chronic administration of morphine.
D000700:Analgesics; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004361:Drug Tolerance; D004723:Endorphins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D019966:Substance-Related Disorders / Q000209:etiology*; D013997:Time Factors
D000700:Analgesics; D004723:Endorphins; D003609:Dactinomycin; D009270:Naloxone; D003513:Cycloheximide