Antidotal effects of buprenorphine on the behavioral alterations accompanying cocaine and combined cocaine-ethanol toxicity.
The present study examined the effects of buprenorphine (BUP), a mixed opioid agonist-antagonist, on the behaviors accompanying cocaine (COCA) and combined cocaine-ethanol (EtOH) toxicity in the surviving mice. Using the activity-counting instrument Supermex, the relationship between the toxic signs and the corresponding behavioral alterations could be assessed. In the COCA-only group, a prolonged increase in the activity counts was caused by a high dose of COCA (75 mg/kg ip). Furthermore, this COCA-induced hyperactivity included ataxic behaviors that were accompanied by visible toxic signs, which were not observed in the mice with no drug treatment. A depressive dose of EtOH (3 g/kg ip) did not significantly modify the mortality rate in the COCA-only group in spite of its anticonvulsant effects. However, the peak activity counts in the survivors were attenuated in the COCA-EtOH group as compared to the COCA-only group. BUP attenuated the mortality rate in both COCA and COCA-EtOH groups, even without any anticonvulsant effects, but the most effective dose differed between the COCA (BUP: 0.25 mg/kg ip) and COCA-EtOH (BUP: 0.5 mg/kg ip) groups. At these BUP doses, the prolonged suppression of the morbid hyperactivity in the COCA-BUP group and the restoration of normal behavior in the COCA-EtOH-BUP group both seemed to be correlated with a good prognosis in the survivors; there was an early recovery from an increased blood pressure (BP), increased heart rate (HR) and decreased respiratory rate (RR) in the COCA-BUP group, and an early recovery from a decreased BP, decreased HR and decreased RR in the COCA-EtOH-BUP group.
Hayase
Tamaki
T
Department of Legal Medicine, Faculty of Medicine, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. hayaselab@jweb.co.jp
Yamamoto
Yoshiko
Y
Yamamoto
Keiichi
K
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002047:Buprenorphine / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000633:toxicity; D003042:Cocaine / Q000633:toxicity*; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity; D004338:Drug Combinations; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009292:Narcotic Antagonists / Q000494:pharmacology; D012131:Respiratory Insufficiency / Q000139:chemically induced; D012640:Seizures / Q000139:chemically induced / Q000401:mortality
D000931:Antidotes; D002492:Central Nervous System Depressants; D018765:Dopamine Uptake Inhibitors; D004338:Drug Combinations; D009292:Narcotic Antagonists; D000431:Ethanol; D002047:Buprenorphine; D003042:Cocaine