Naltrexone, naltrindole, and CTOP block cocaine-induced sensitization to seizures and death.
I.c.v. injection for 9 days of either naltexone (NTX) (5, 10, 20, 40 micrograms/rat) or a selective mu peptide (CTOP) (0.125, 0.25, 0.5, 1, 3, 6 micrograms/rat) or delta (naltrindole) (NLT) (5, 10, 20 micrograms/rat) subtype opioid receptor antagonist affected sensitization to cocaine (COC) (50 mg/kg, i.p.) administered 10 min after. NTX (5 and 40 micrograms/rat), NLT (10 and 20 micrograms/rat), and the peptide CTOP (0.25-0.5 microgram/rat) attenuated seizure parameters (percent of animals showing seizures, mean score and latency) in a day-related manner. The DD50 (days to reach 50% of death) value for COC was 2.69, whereas it was 9.67 and 7.27 for NTX 5 and 40 micrograms/rat, 8.59 for NLT (10 micrograms/rat), and 6.11, 5.95, and 4.30 for CTOP (0.25, 0.5, and 1 microgram/rat respectively). These findings suggest a concurrent involvement of mu- and delta-opioid receptor subtype in COC-induced sensitization to toxic effects.
Braida
D
D
Institute of Pharmacology, Faculty of Mathematical, Physical and Natural Sciences, University of Milan, Italy.
Paladini
E
E
Gori
E
E
Sala
M
M
D000818:Animals; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology
D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; D009271:Naltrexone; C055382:naltrindole