Neuropeptides differentially effect various forms of morphine tolerance.
Two different forms of tolerance to morphine were shown to develop. One form, environment dependent (ED), was associated with cues paired with the arrival of the drug. The second form of tolerance, environment independent (EI), was not dependent on any cues. ED tolerance was induced using a multiple injection model in which a cue (orange scent) preceeded each morphine injection (ip). After 12 days the animals were tolerant to the i.p. injection. However if morphine was injected i.c.v. tolerance was no longer evident. EI tolerance was induced by a pellet implant method. These animals were tolerant to morphine regardless of the route of administration. Peptides arginine vasopressin (AVP) and cyclo (Leu-Gly) (cLG) were tested for their ability to alter tolerance. AVP was found to facilitate the development of ED tolerance but had no effect on EI tolerance. On the other hand cLG blocked the development of EI tolerance without affecting ED tolerance. The determination of brain morphine levels indicated that the ED tolerance produced by this method is dispositional while EI tolerance is functional.
D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage*; D003463:Cues; D004151:Dipeptides / Q000008:administration & dosage*; D004347:Drug Interactions; D004361:Drug Tolerance; D004777:Environment; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D009479:Neuropeptides; D010456:Peptides, Cyclic
D004151:Dipeptides; D009479:Neuropeptides; D010456:Peptides, Cyclic; D001127:Arginine Vasopressin; C021166:cyclo(leucylglycine); D009020:Morphine