Tolerance to the hypothermic but not to the analgesic effect of [D-Trp11]neurotensin during the semichronic intracerebroventricular infusion of the peptide in rats.
The peptidase-resistant derivative of neurotensin, [D-Trp11]neurotensin, has been continuously infused intracerebroventricularly (75 ng/h) with an osmotic minipump for 10 days. On several days during this infusion the locomotor activity, the body temperature, the food intake, the body weight, and the nociceptive response in the plantar test were measured. A nonsignificant decrease of body temperature and a sustained analgesic effect were observed at each time considered. The response to a test dose of [D-Trp11]neurotensin (75 ng per rat) injected intracerebroventricularly at the 10th day of the chronic infusion revealed a complete tolerance to its hypothermic effect. Thus, it appears that the analgesic effect of [D-Trp11]neurotensin is independent of a hypothermic or an incapacitating effect of the peptide and does not give rise to tolerance after a 10-day continuous administration, in contrast to the hypothermic effect.
Dubuc
I
I
European Institute for Peptide Research, Unité de Neuropsychopharmacologie Expérimentale U.R.A. 1170 du C.N.R.S., Faculté de Médecine et Pharmacie de Rouen, Saint Etienne du Rouvray, France.
Pain
C
C
Suaudeau
C
C
Costentin
J
J
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004361:Drug Tolerance; D004435:Eating / Q000187:drug effects; D007035:Hypothermia / Q000139:chemically induced*; D007260:Infusion Pumps; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009496:Neurotensin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000700:Analgesics; D009496:Neurotensin; C024309:neurotensin, Trp(11)-