Naltrexone, naltrindole, and ctop block cocaine-induced sensitization to seizures and death

ICV injection for 9 days of either naltexone (NTX) (5, 10, 20, 40 mu g/rat) or a selective mu peptide (CTOP) (0.125, 0.25, 0.5, 1, 3, 6 mu g/rat) or delta (naltrindole) (NLT) (5, 10, 20 mu g/rat) subtype opioid receptor antagonist affected sensitization to cocaine (COG) (50 mg/kg, IP) administered 10 min after. NTX (5 and 40 mu g/rat), NLT (10 and 20 mu g/rat), and the peptide CTOP (0.25-0.5 mu g/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 mu g/rat, 8.59 for NLT (10 mu g/rat), and 6.11, 5.95, and 4.30 for CTOP (0.25, 0.5, and 1 mu g/rat respectively). These findings suggest a concurrent involvement of mu- and delta-opioid receptor subtype in COC-induced sensitization to toxic effects.