Physiology&Behavior. Vol. 54, pp. 753-758, 1993 0031-9384/93 $6.00 + .00 Printed in the USA. Copyright © 1993 Pergamon Press Ltd. Role of Resocialization and of 5-HT1A Receptor Activation on the Anxiogenic Effects Induced by Isolation in the Elevated Plus-Maze Test S. MAISONNETTE, S. MORATO AND M. L. BRANDAO l Laboratory of Psychobiology, Faculdade de Filosofia, Ci~ncias, e letras de Ribeir~o Preto, Campus-USP, 4040-901, Ribeir~o, Preto, S~o Paulo, Brazil Received 14 January 1993 MAISONNETTE, S., S. MORATO AND M. L. BRANDAO. Role of resocialization and of 5-TH1A receptor activation on the anxiogenic effects induced by isolation in the elevated plus-maze test. PHYSIOL BEHAV 54(4) 753-758, 1993.--Rats were isolated for periods varying from 1 h to 2 weeks and the exploratory activity of these animals on the elevated plus-maze was studied. Rats isolated from periods of 2 h on displayed a significant reduction in the number of entries and time spent in the open arms of the plus-maze compared to socially housed controls. This effect was not correlated with the decrease in the total number of entries also produced by isolation. Acute treatment with midazolam or resocialization for a 24-h period clearly reversed these responses produced by prior 2-h isolation in the elevated plus-maze. It is suggested that exposure to a 2-h isolation period could be a useful nonpharmacological means of generating anxiety in laboratory rodents. Chronic treatment, but not acute treatment, with gepirone, a 5-HTtA agonist, inhibited the anxiogenic effects caused by a 2-week period of isolation. The reduction in aversiveness promoted by resocialization may be due to a recovery in the 5-HT activity depressed by isolation in a much faster way than observed with chronic gepirone administration. Isolation Resocialization 5-HTIA receptors Gepirone Elevated plus-maze Aversion ISOLATED rats demonstrate many behavioral disturbances such as increased locomotor activity, neophobia, deficits in learning involving or not spatial memory, and aggressive muricidal be- havior (20,28,33). Neophobia and some of the other behavioral differences observed in isolation-reared animals are thought to be related to increased anxiogenic profile, and a raised level of anxiety is observed when isolation-reared rats are placed in a novel environment (23). Recently we have shown that the iso- lation of rats for 2 weeks causes increased anxiety-related be- havior in the elevated plus-maze test (21). In the present work we were interested in examining what was the minimum period of isolation capable of producing these anxiety effects in the elevated plus-maze and also the minimal period ofresocialization necessary to reverse them. Previous research has suggested that brain serotonergic neu- rotransmitter system participates in the modulation of anxiety [for reviews see (13,14,16)], and that isolation is accompanied by changes in the activity of this system (28,31). 5-HTIA agonists like gepirone, as well as the benzodiazepines, all suppress neu- ronal activity in the dorsal raphe nucleus following either sys- temic or iontophoretic administration (3,1 1,30). Gepirone, which binds with high affinity to the 5-HTIA receptor subtype (27), has been reported to be clinically as effective as the standard ben- zodiazepine, diazepam, as an anxiolytic (5). It has been shown that upon acute administration the presynaptic effect ofgepirone, which causes a reduction of 5-HT neuron activity, overrides its postsynaptic action, an effect that results in a net decrease of the serotonergic tone (19). However, it has been observed that sustained administration of gepirone is necessary to attain a clinically significant relief of anxiety (5). Based on these data, we also carried out a comparative study of the effects ofgepirone, acutely and chronically administered, and midazolam, a known benzodiazepine agent, on the performance of socially isolated rats in the elevated plus-maze. METHOD Animals Male Wistar rats, weighing 220-250 g, were housed in groups of six with free access to food and water. They were kept in groups of six (except when stated otherwise) in cages of 60 × 60 × 30 cm for 72 h prior to the experiment, on a 12 h light:dark cycle (lights on at 0700 h) in a room adjacent to the experimental room. The temperature in both rooms was maintained between 25 and 27°C. ' Requests for reprints should be addressed to M. L. Brand~o. 753