Pharmacology Biochemistry &Behavior, Vol. 37. pp. 89-93. ©Pergamon Press plc, 1990. Printed in the U.S.A. 0091-3057/90 $3.00 + .00 Effects of Apomorphine on Novelty-Induced Place Preference Behavior in Rats M. T. BARDO,* M. LACY* AND B. A. MATTINGLYt *Department of Psychology, University of Kentucky, Lexington, KY 40506 ~-Department of Psychology, Morehead State University, Morehead, KY 40351 Received 6 February 1990 BARDO, M. T., M. LACY AND B. A. MATrlNGLY. Effects of apomorphineon novelty-induced placepreference behaviorin rats. PHARMACOL BIOCHEM BEHAV 37(1) 89-93, 1990.--Adult male rats were exposed to one of two different stimulus compartments by being placed into the compartment for 30 min on each of eight consecutive days. Following this exposure, each rat was administered 0, 0.05, 0.1, 0.5 or 5.0 mg/kg apomorphine. Thirty min after injection, each animal was given free-choice access to the familiar (exposed) compartment and to the novel (nonexposed) compartment. As expected, saline-injected control animals displayed a preference for the novel compartment. This novelty preference was disrupted in animals given either 0.05 or 0.1 mg/kg apomorphine, but not in animals given either 0.5 or 5.0 mg/kg apomorphine. The disruption in novelty preference by the low doses of apomorphine did not reflect a disruption of locomotor activity, as there was no direct relationship between the preference for novelty and the rate of horizontal or vertical activity among the different treatment groups. Instead, the low doses of apomorphine may have inhibited dopamine function by blocking presynaptic autoreceptors selectively, and thus the reinforcing effect of the novel stimulation may have been attenuated. Place preference Apomorphine Novelty Locomotor activity Dopamine EXPOSURE to novel environmental stimuli may activate the mesolimbic dopamine (DA) pathway in a manner analogous to the administration of stimulant drugs. Similar to the effects of am- phetamine, rats exposed to novel environmental stimuli display an increase in locomotor activity (2, 3, 28) and find novel stimuli to be reinforcing as assessed in the place preference paradigm (6, 11, 23). Lesions of the mesolimbic DA system disrupt the increase in locomotion, rearing and approach behaviors normally elicited by novel stimuli (7, 8, 19). Further, novelty-induced place preference is blocked when rats or mice are tested under the influence of DA antagonist drugs such as haloperidol and thio- ridazine (1,18). While DA antagonists disrupt novelty-induced place prefer- ence, the effect of DA agonists on novelty preference behavior is less clear. Methamphetamine has been reported to decrease novelty preference behavior as either a direct function of dose (17) or as a U-shaped function of dose (12). More recently, our laboratory failed to detect any effect of d-amphetamine (0.1-1.0 mg/kg) on novelty-induced place preference (1). The lack of effect obtained with d-amphetamine may reflect the relatively weaker action of this drug compared to methamphetamine within the central nervous system (27). However, other methodological differences between experiments cannot be ruled out. The purpose of the present experiment was to examine the effect of the direct DA agonist apomorphine on novelty-induced place preference behavior in rats. Unlike the indirect DA agonist amphetamine, which evokes the release of DA from presynaptic terminals, apomorphine has a a direct agonist action at both presynaptic and postsynaptic receptors (24). We chose a range of apomorphine doses (0, 0.05, 0.1,0.5 and 5.0 mg/kg) which would presumably assess both the low- and high-dose receptor actions of apomorphine. METHOD Animals The animals were male Sprague-Dawley rats obtained from Harlan Industries (Indianapolis, IN) at 225-250 g body weight. Animals were caged individually with food and water available continuously in the home cage. Prior to the start of the experiment, animals were acclimated to the colony room (22 - I°C, humidity 45 ---5%) for at least one week and were handled for 2 days. Apparatus The apparatus consisted of a rectangular wooden chamber that had three different compartments separated by removable parti- tions. The two end compartments measured 24 x 30 x 45 cm high, while the middle compartment was smaller and measured 24 x 10 x 45 cm high. One end compartment had white walls, a wire mesh floor, and pine bedding beneath the floor. The other end compartment had black walls, a metal grid floor, and cedar bedding beneath the floor. The middle compartment had gray walls and a solid wood floor. The solid partitions could be 89