Pharmacology Biochemistry and Behavior, Vol. 65, No. 2, pp. 209–216, 2000 © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0091-3057/00/$–see front matter PII S0091-3057(99)00193-8 209 Acute and Chronic Effects of Gepirone and Fluoxetine in Rats Tested in the Elevated Plus-maze: An Ethological Analysis R. C. B. SILVA AND M. L. BRANDÃO Laboratório de Psicobiologia, Dept. de Psicologia, FFCLRP-USP, Campus, AV. Bandeirantes, 3900, 14049-901 Ribeirão Preto, São Paulo, Brazil Received 11 December 1998; Revised 26 April 1999; Accepted 4 June 1999 SILVA, R. C. B. AND M. L. BRANDÃO. Acute and chronic effects on gepirone and fluoxetine in rats tested in the ele- vated plus-maze: An ethological analysis. PHARMACOL BIOCHEM BEHAV 65(2) 209–216, 2000.—The potential role of 5-hydroxytryptamine (5-HT) in anxiety has been the subject of much research, most of it addressed to the hypothesis that 5- HT promotes anxiety and, therefore, that drugs that reduce 5-HT functions will be effective anxiolytic agents in human anxi- ety disorders. However, the effects of serotoninergic drugs in different behavioral paradigms have been inconsistent. These inconsistencies have been particularly well illustrated in the elevated plus-maze. In the present study we provided an ethop- harmacological analysis (in addition to conventional measures) of the behavior of rats in the elevated plus-maze with trans- parent walls after acute and chronic treatments with gepirone, an agonist of 5-HT 1A receptors, and fluoxetine, a selective in- hibitor of serotonin reuptake. Although gepirone has been used to treat anxiety, fluoxetine is a mainstay in the treatment of depression. Acute treatment with gepirone (1, 3, 5.6, and 10 mg/kg, IP) produced an anxiogenic profile with increased risk as- sessment behaviors (e.g., flat-back approach) and decreased behavioral measures that are inversely related to “anxiety” (e.g., head dipping and end-arm activity). In contrast, chronic gepirone (10 mg/kg day, PO) produced an opposite effect showing an anxiolytic profile that is consistent with the clinical use of this drug, which shows efficacy after 2–4 weeks of treatment. Acute fluoxetine (5.6 and 10 mg/kg, IP) also produced an anxiogenic profile with reduced head dipping and end-arm activity. On the other hand, chronic fluoxetine (10 mg/kg day, PO) had no effect on any of the behavioral measures. These data demonstrate: (a) the anxiogenic and anxiolytic effects of acute and chronic gepirone, respectively, corroborate with the observed effects of these treatments in the clinic; (b) similarly, the anxiogenic effects of acute fluoxetine observed here have also been reported in clinical studies with 5-HT reuptake blockers. This class of compounds has not been systematically used as anxiolytic; (c) the elevated plus-maze with transparent walls shows good sensitivity for evaluating serotonergic drugs with anxiogenic and anxi- olytic profile. © 2000 Elsevier Science Inc. Elevated plus-maze Ethological analysis Gepirone Fluoxetine Rat Thigmotaxis ANIMAL models of anxiety are used as screening tools in the search for compounds with therapeutic potential and as stim- ulations for research on mechanisms underlying emotional behavior (34). The elevated plus-maze is one of the most widely used animals models in contemporary preclinical re- search on anxiety (16,19,32). This model is based on the in- nate fear rodents have for open and elevated spaces (23). Rats on the elevated plus-maze tend to avoid the open arms and prefer to stay in the enclosed arms. When confined to the open arms, rats show behavioral and physiological manifesta- tions of fear, such as freezing, defecation, and increases in plasma corticosteroids (28,38). The avoidance of the open arms occurs primarily because they prevent the rat from en- gaging in thigmotaxic behavior (38). Thigmotaxis is a natural defensive response that keeps the rat in contact with a vertical surface, thereby avoiding predators (36,38). Requests for reprints should be addressed to M. L. Brandão, Laboratório de Psicobiologia, Dept. de Psicologia, FFCLRP-USP, Campus, AV, Bandeirantes, 3900, 14049-901 Ribeirão Preto, São Paulo, Brasil.