Anxiolytic and anticonvulsant properties of doramectin in rats: behavioraland neurochemistric evaluations

Doramecin is an antiparasitic drug that may interfere with gamma-aminobutyr ic acid (GABA) neurotransmission. Some behavioral manifestations are relate d with GABAergic neurotransmissions as anxiety and seizures. The objective of the present study was to examine the possible central nervous system (CN S) effects of doramectin (100, 300 and 1000 mug/kg, SC) in rats, using anxi ety behavioral models, susceptibility to seizures and central neurotransmit ter evaluations. The open-field results showed (i) few alterations in locom otion frequency; (ii) a biphasic effect on rearing frequency that may be th e consequence of least habituation in open-field; (iii) the reduction of gr ooming durations might be attributed to a possible anxiolytic effect of dor amectin since GABAergic agonists reduced this parameter in apparatus. Our d ata in the hole board showed no effects in locomotion and rearing frequenci es but increased head dipping frequency of rats administered doramectin sim ilarly to anxiolytic drugs. In plus-maze test, doramectin administration in creased the number of entries and time into open arms, indicating also an a nxiolytic effect. Doramectin protected animals from convulsant effects of p icrotoxin, indicative of an anxiolytic pharmacological profile of a drug wi th GABAergic properties. The alterations observed in central dopaminergic, noradrenergic and serotoninergic neurotransmissions might be the consequenc e of reinforcement in central GABAergic neurotransmission induced by dorame ctin. The present results suggest that doramectin has the pharmacological p rofile of an anxiolytic/anticonvulsant drug with GABAergic properties. (C) 2000 Elsevier Science Inc. All rights reserved.