Pergamon 0031-9384(94)00209-6 Physiology & Behavior, Vol. 57, No. I, pp. 55-59, 1995 Copyright © 1994 ElsevierScienceLtd Printed in the USA. All rights reserved 0031-9384/95 $9,50 + .00 Perseveration Without Hyperlocomotion in a Spontaneous Alternation Task in Rats Sensitized to the Dopamine Agonist Quinpirole HAIM EINAT* AND HENRY SZECHTMAN5 "l *Department of Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5 and ~Departments of Biomedical Sciences, Psychiatry, and Psychology, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5 Received 10 December 1993 EINAT, H. AND H. SZECHTMAN. Perseveration without hyperlocomotion in a spontaneous alternation task in rats sensitized to the dopamine agonist quinpirole. PHYSIOL BEHAV 57(1) 55-59, 1995.--Behavioral sensitization induced by intermittent injections of the dopamine agonist quinpirole is characterized by hyperlocomotion and perseveration. This study tested whether in sensitized rats, the expression of perseverative behavior can be independent of hyperlocomotion. Rats received 10 injections of either quinpirole (0.5 mg/kg) or saline in a T-maze apparatus, a procedure that induced locomotor sensitization in the drugged animals. When tested later (under quinpirole) for spontaneous alternation in the same T-maze, in a discrete trial procedure, sensitized rats showed decreased spontaneous alternation, compared either to saline controls or acute quinpirole. The decrease in spontaneous alternation showed a tendency to be lower than chance level of alternation, suggesting perseveration. The possibility is discussed that the sensitization-reduced spontaneous alternation may relate to a diminution in the sense of task completion, and the increased perseveration may model a form of compulsive "checking" shown in obsessive-compulsive disorder. Behavioral sensitization Path stereotypy Obsessive-compulsive disorder Hyperactivity T-maze Animal model CHRONIC treatment in rats with the dopamine (D2]D3) agonist quinpirole induces marked hyperlocomotion and stereotypy in the patterning of activity. The amount of locomotion increases about six-fold compared to an acute injection, and path stereotypy (the tendency to travel along the same route in an open field) rises more than two-fold (26-28), with increases in locomotor hyperactivity preceding the rise in path stereotypy (27). The co-occurrence of hypeflocomotion and path stereotypy, and their temporal relation- ship, have led to the suggestion that reduced variability in patterning of locomotion is a necessary consequence of the drug-induced hy- peractivity and is not a primary effect of the drug (6,8,25,27). Yet, other studies suggest that hyperactivity and perseverative responding (rigidity) may be expressed independently. In particular, the un- drugged behavior of rats sensitized to quinpirole is marked by re- duced behavioral flexibility on a variety of tasks, without apparent signs of hyperactivity (8). Moreover, under amphetamine at least, there is evidence that perseveration can be present without hyper- locomotion (1,13). It is not known however whether such persev- erative behavior without concurrent hyperlocomotion can also be present under quinpirole. To examine this possibility, the present study utilized a spontaneous alternation paradigm. Spontaneous alternation refers to the tendency of rats to ex- plore novel places sequentially and in succession; thus in a T-maze, rats tend to visit one arm, and then another one (3,12,19,23). Previous studies suggest that spontaneous alterna- tion is in fact reduced by dopaminergic drugs, including am- phetamine (e.g. 1,13), apomorphine (16) and SKF38393 (18), and in a manner that is dissociable from drug effects on loco- motion (1,13). Although the dissociation between hyperloco- motion and perseveration had been shown using continuous ex- ploration in a Y-maze (1,13), in the present study we utilize a paradigm of discrete trials in a T-maze. Testing rats in a T-maze fixes across groups the distance of travel and constrains the speed of locomotion, thereby permitting assessment of perseveration without the expression of hyperlocomotion. METHOD Subjects Twenty two experimentally naive male Long-Evans rats (Charles River, Canada), weighed 200-230 g at the start of the experiment. They were housed singly in polyethylene cages (35 1Requests for reprints should be addressed to Dr. Henry Szechtman, Department Biomedical Sciences, McMaster University, 1200 Main St. West, Hamilton, Ontario, Canada L8N 3Z5. E-mail: Szechtma@FHS.McMaster.ca 55