Comparative Biochemistry and Physiology Part C 127 (2000) 359 – 366 Anxiolytic and anticonvulsant properties of doramectin in rats: behavioral and neurochemistric evaluations Helenice de Souza Spinosa *, Marli Gerenutti, Maria Martha Bernardi Department of Pathology, Faculty of Veterinary Medicine and Zootechny, Uniersity of Sa ˜o Paulo, Aenue Professor Dr Orlando Marques de Paia, 87 CEP 05508 900 Sa ˜o Paulo, Brazil Received 30 May 2000; received in revised form 8 September 2000; accepted 21 September 2000 Abstract 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 g/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. © 2000 Elsevier Science Inc. All rights reserved. Keywords: Avermectins; Behavior; Central nervous system; Doramectin; Neurotransmitters; GABA; Dopamine; Norepinephrine; Serotonin www.elsevier.com/locate/cbpc 1. Introduction The avermectins (ivermectin and abamectin) are produced through fermentation by soil dwelling actinomycetes from the genus Streptomyces.A new avermectin doramectin, 25-cyclohexyl-5-0- demethyl-25-de (1-methylpropyl) avermectin A 1a , was selected as the best of a series of novel avermectins prepared by mutational biosynthesis. It is used as a potent novel veterinary endectocide, i.e. it is a combination killing of endo- and ecto- parasites (Goudie et al., 1993). Evidences showed that doramectin has effects on central nervous system (CNS), since doramectin, like ivermectin and other drugs in this class affect gamma-aminobutyric acid (GABA)-sensitive neurons, which can lead to neu- rotoxicity, as tremors, ataxia and gait abnormali- ties. Turner and Schaeffer (1989) summarized the * Corresponding author. Tel.: +55-11-38187656; fax: +55- 11-38187829. E-mail address: hspinosa@usp.br (H. de Souza Spinosa). 0742-8413/00/$ - see front matter © 2000 Elsevier Science Inc. All rights reserved. PII:S0742-8413(00)00165-1