Interactions between NTS2 neurotensin and opioid receptors on two nociceptive responses assessed on the hot plate test in mice.
The intracerebroventricular administration of the tridecapeptide neurotensin (NT) produces strong analgesic effects in tests evaluating acute pain. We investigated whether these effects are mediated by the opioid receptors. In the hot plate test, the NT receptors agonist NT1 (N(alpha)Me-Arg-Lys-Pro-Trp-Tle-Leu), s.c. injected (0.3-3 mg/kg), increased paw licking and jump latencies. These effects were inhibited by the NTS2 antagonist levocabastine (2.5 mg/kg, i.p.) but not by the selective NTS1 antagonist SR48692 (3 mg/kg, i.p.). The opioid receptor antagonist naloxone did not modify (up to the dose of 4.5 mg/kg, s.c.) the NT1 effect on licking, but abolished the increase in the jump latency (from the dose of 1.5 mg/kg). In mice made tolerant to the analgesic effect of morphine (2 mg/kg, s.c.) by previous morphine injections (32 mg/kg, s.c., twice a day, 4 days), NT1 maintained its effect on licking, but its effect on jump latency was suppressed. Levocabastine (up to the dose of 4.5 mg/kg) failed to antagonize the effects of morphine (2 mg/kg, s.c.) on both licking and jump latencies. In mice made tolerant to the analgesic effect of NT1 (0.3 mg/kg, s.c.) by previous NT1 injections (3 mg/kg, s.c., twice a day, 4 days) morphine maintained its analgesic effects both on licking and jumping latencies. We can conclude that neurotensinergic and opioidergic transmissions are functionally independent as regards the licking response. However, in the jump response, neurotensinergic transmission seems to regulate opioidergic transmission, inducing its stimulation.
Bredeloux
Pierre
P
CNRS FRE 2735, Unité de Neuropsychopharmacologie Expérimentale, IFRMP 23, Faculté de Médecine-Pharmacie, 22 Bd Gambetta, 76183 Rouen Cedex, France.
Costentin
Jean
J
Dubuc
Isabelle
I
D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage; D007276:Injections, Intraventricular; D008024:Ligands; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009496:Neurotensin / Q000008:administration & dosage / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage; D011804:Quinolines / Q000008:administration & dosage; D011930:Reaction Time; D018028:Receptors, Neurotensin / Q000187:drug effects / Q000378:metabolism*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*
D000701:Analgesics, Opioid; D039563:Histamine H1 Antagonists, Non-Sedating; D008024:Ligands; C490984:Ntsr2 protein, mouse; D010880:Piperidines; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; D011957:Receptors, Opioid; C114036:neurotensin type 1 receptor; C079087:SR 48692; D009496:Neurotensin; D009020:Morphine; C047340:levocabastine