Anxiolytic and anticonvulsant properties of doramectin in rats: behavioral and neurochemistric evaluations.
Doramecin is an antiparasitic drug that may interfere with gamma-aminobutyric acid (GABA) neurotransmission. Some behavioral manifestations are related with GABAergic neurotransmissions as anxiety and seizures. The objective of the present study was to examine the possible central nervous system (CNS) effects of doramectin (100, 300 and 1000 microg/kg, SC) in rats, using anxiety behavioral models, susceptibility to seizures and central neurotransmitter evaluations. The open-field results showed (i) few alterations in locomotion frequency; (ii) a biphasic effect on rearing frequency that may be the consequence of least habituation in open-field; (iii) the reduction of grooming durations might be attributed to a possible anxiolytic effect of doramectin since GABAergic agonists reduced this parameter in apparatus. Our data in the hole board showed no effects in locomotion and rearing frequencies but increased head dipping frequency of rats administered doramectin similarly to anxiolytic drugs. In plus-maze test, doramectin administration increased the number of entries and time into open arms, indicating also an anxiolytic effect. Doramectin protected animals from convulsant effects of picrotoxin, indicative of an anxiolytic pharmacological profile of a drug with GABAergic properties. The alterations observed in central dopaminergic, noradrenergic and serotoninergic neurotransmissions might be the consequence of reinforcement in central GABAergic neurotransmission induced by doramectin. The present results suggest that doramectin has the pharmacological profile of an anxiolytic/anticonvulsant drug with GABAergic properties.
Department of Pathology, Faculty of Veterinary Medicine and Zootechny, University of São Paulo, São Paulo, Brazil. hspinosa@usp.br
H
H
de Souza Spinosa
M
M
Gerenutti
M M
MM
Bernardi
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D003292:Convulsants / Q000633:toxicity; D005260:Female; D006120:Grooming / Q000187:drug effects; D007559:Ivermectin / Q000031:analogs & derivatives / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D010852:Picrotoxin / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D003292:Convulsants; D007559:Ivermectin; D018377:Neurotransmitter Agents; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid; C084101:doramectin