Intraventricular administration of BAM-18: antinociceptive and locomotor activity in the rat.
BAM-18, a new endogenous opioid containing 18 amino acid residues, was tested in 3 behavioral paradigms. Tail-flick analgesia, a spinally mediated response, hot-plate analgesia, a centrally mediated response, and open-field locomotor activity. Rats were stereotaxically implanted with a unilateral cannula aimed at the lateral ventricle. Following recovery, each animal was tested in one of the paradigms after receiving an intraventricular injection of BAM-18, morphine or the Ringer's vehicle. BAM-18 produced significant tail-flick analgesia only at doses (50 micrograms) 50 times higher than those needed with morphine (1 microgram). BAM-18 produced an extended hyperalgesia at lower doses (5 micrograms) that was also seen transiently at the high dose. The analgesia but not the hyperalgesia was reversed by naloxone (10 mg/kg, s.c.). BAM-18 produced significant naloxone-reversible hot-plate analgesia, but again it was less potent than morphine (50 micrograms for BAM-18 vs. 5 micrograms for morphine). There was no evidence of hyperalgesia in this paradigm. Locomotor activity, following 50 micrograms of BAM-18, resembled control injections for the first 18 minutes, then became reduced in a manner similar to morphine (5 micrograms). This reduction in activity was completely reversed by naloxone. These data suggest that BAM-18 is indeed an opioid molecule but is at least 10 times less potent at altering behavior than morphine.
D000698:Analgesia; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011498:Protein Precursors; C053492:BAM 18P; D004744:Enkephalin, Methionine