Possible anxiolytic effects of ivermectin in rats.
Ivermectin, a mixture of 22,23-dihydroavermectin B1a (> or = 80%) and B1b (< or =20%), is produced by Streptomyces avermectilis, an actinomycete. It is a macrocyclic lactone disaccharide, a member of the avermectin family, and is used as an antiparasitic drug. Previous studies performed in our laboratory showed that doramectin, another avermectin drug, interferes with GABAergic-related behaviours, leading to anxiety and seizures. The objective of the present study was to examine the effects of ivermectin (0.5 and 1.0 mg/kg) on the central nervous system of rats, using behavioural models related to GABAergic neurotransmission. A known anxiolytic drug, diazepam, was used as a positive control. Open field and elevated plus-maze behaviours, as well as conflict behaviour to a conditioned response, were assessed. The effects of ivermectin and diazepam in reversing the anxiety induced by picrotoxin was studied. The protective effects of ivermectin on pentylenetetrazole- and picrotoxin-induced seizures were also investigated. In the open field, 1.0 mg/kg ivermectin decreased locomotion frequency at 15 and 60 min of observation, rearing behaviour showed a biphasic effect at 15 and 30 min and duration of immobility was increased in all sessions after 1.0 mg/kg ivermectin. These data suggest anxiolytic or sedative effects. Ivermectin and diazepam both had a tendency to cause an increase both in the number of entries into the open arms and on the time spent in the open arms of an elevated plus-maze. Picrotoxin on its own reduced the number of entries as well as the time spent in the open arms. Both diazepam and ivermectin reversed these effects of picrotoxin. In conflict behaviour analysis, ivermectin and diazepam gave the classic effect of an anxiolytic drug, reversing the conditioned response to shock. Ivermectin protected rats from the convulsant effects of pentylenetetrazole but not from those of picrotoxin. Thus, ivermectin had the pharmacological profile of an anxiolytic drug with GABAergic properties. The lack of effect on seizures induced by picrotoxin suggests that the action of ivermectin is different from that of the benzodiazepine drugs.
Department of Pathology, Faculty of Veterinary Medicine and Zootechny, University of São Paulo, Brazil. hspinosa@usp.br
H de Souza
Hde S
Spinosa
S R A N
SR
Stilck
M M
MM
Bernardi
D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000494:pharmacology*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D007559:Ivermectin / Q000009:adverse effects / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D003975:Diazepam; D007559:Ivermectin; D010852:Picrotoxin