Locomotor and analgesic effects of morphine and acetorphan in rats chronically treated with morphine or thiorphan.
A continuous 8-day s.c. administration of morphine (450 microgram/kg/h) sensitized rats to the morphine-induced stimulation of locomotion (morphine test dose = 3 mg/kg, s.c.) but not to the acetorphan (5 mg/kg, i.v.)-induced stimulation of locomotion. On the other hand, a continuous 10-day intracerebroventricular infusion of the enkephalinase inhibitor, thiorphan (25 micrograms/rat/h), known to desensitize the acetorphan-induced stimulation of locomotion, also desensitized the morphine (3 mg/kg, s.c.)-induced stimulation of locomotion. The continuous 10-day, s.c. administration of morphine desensitized to the morphine (3 mg/kg, s.c.)-but not acetorphan (5 mg/kg, i.v.)-induced analgesia, as measured by the latency to jump from a hot plate (55 degrees C). On the other hand, the continuous 10-day intracerebroventricular infusion of thiorphan did not desensitize to morphine (3 mg/kg, s.c.)-induced analgesia. Thus, the chronic actions of morphine and thiorphan, according to the tested function, did not result in cross-sensitization (locomotion) or cross-tolerance (nociception). These differences could depend on the involvement of different opioid receptors (mu vs. delta) and/or on different functional organizations.
Khallouk-Bousselmame
R
R
Unité de Neuropsychopharmacologie Expérimentale, U.R.A. 1170 du C.N.R.S., European Institute for Peptide Research, Faculté de Médecine & Pharmacie de Rouen, Saint-Etienne du Rouvray, France.
Costentin
J
J
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015244:Thiorphan / Q000031:analogs & derivatives* / Q000494:pharmacology
D000700:Analgesics; D009020:Morphine; C049331:racecadotril; D015244:Thiorphan