Pergamon Pharmacology Biochemistry and Behavior,Vol. 47, No. 3. pp. 427-435, 1994 Copyright© 1994Elsevier Science Ltd Printed in the USA.All rights reserved 0091-3057/94 $6.00 + .00 Effects of Chronic Imipramine on Exploration, Locomotion, and Food/Water Intake in Rats JESPER MOGENSEN, t THOMAS KIRK PEDERSEN AND SOREN HOLM Laboratory of Neuropsychiatry, Department of Pharmacology, University of Copenhagen, Denmark Received 23 March 1993 MOGENSEN, J., T. K. PEDERSEN AND S. HOLM. Effects of chronic imipramine on exploration, locomotion, and food~water intake in rats. PHARMACOL BIOCHEM BEHAV 47(3) 427-435, 1994.--Three groups of rats were subjected to 15 daily injections of imipramine (10 or 20 mg/kg) or vehicle control injections, respectively. During the treatment period, both imipramine groups failed to grow while the control group gained weight normally. Both dosages of imipramine sup- pressed food intake significantly, while water intake was only reduced by 20 mg/kg of imipramine and only during the first 5 days of treatment. Twenty-four hours after the last imipramine injection, the animals were subjected to a test battery designed to demonstrate potential changes in locomotion and/or exploration. While locomotion appeared unaffected by both dosages of imipramine, the group receiving 20 mg/kg of imipramine demonstrated a significantly reduced exploration. The exploration of the group receiving imipramine in the concentration of 10 mg/kg was only marginally changed. The temporal pattern of exploration of the animals receiving 20 mg/kg of imipramine revealed that chronic imipramine treatment was associated with an initial "hyperexploration" followed by an "overhabituation," resulting in an overall reduction of exploration during a 15-min period. Imipramine Food intake Water intake Body weight Exploration Locomotion Rat Habituation Chronic drug administration THE tricyclic antidepressant imipramine blocks the reuptake of serotonin and norepinephrine (18). Long-lasting or chronic administration of imipramine has, in the rat, been found to be associated with decreased (1,3,4,9,15) or unchanged (7,13,14) locomotion if the behavioural test is performed within the first few hours following the last injection. Studies in which locomotion has been tested at least 12 h after the last imipra- mine injection demonstrate locomotion to be unaffected (12,17) or increased (15) by chronic imipramine administra- tion. Based on a review of the effects of chronically adminis- tered antidepressant drugs, Vogel et al. (19) suggested that while each individual dose of tricyclic antidepressants inhibits motor activity for a few hours after injection, chronically ad- ministered antidepressants, such as imipramine, increase mo- tor activity 12-24 h after each administration. When tested immediately upon the last imipramine injection, measures be- lieved to reflect exploration have been found to be increased (13), reduced (9), or unaffected (8) by chronic administration of imipramine to the rat. When tested 48 h upon the last imipramine injection, measures of exploration appeared unaf- fected by chronic imipramine administration (17). As argued by Hughes and Pither (9), the observations that seem to indicate an association between chronic imipramine treatment and reduced exploration may be secondary to imip- ramine-induced reduction of locomotion and general activity. Consequently, to study the degree to which exploration is in- fluenced by chronic administration of imipramine, it is neces- sary to measure the exploration of imipramine-treated rats using apparatuses and procedures able to reflect exploratory behaviour without being significantly influenced by changes in locomotion. Using an exploration test believed to be rather unaffected by changed locomotor behaviour, Hughes and Pitcher (9) found chronic imipramine treatment to have no influence on exploratory behaviour 30 min after the last imip- ramine injection. In an attempt to further clarify the effects of chronic imip- Requests for reprints should be addressed to Jesper Mogensen, Laboratory of Neuropsychiatry, Rigshospitalet-6102, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark. 427