PharmacologyBiochemistry& Behavior, Vol. 36, pp. 521-525. ©Pergamon Press plc, 1990. Printed in the U.S.A. 0091-3057/90 $3.00 + .00 Opiate Antagonists Enhance the Working Memory of Rats in the Radial Maze TURHAN CANLI,t ROBERT G. COOK AND KLAUS A. MICZEK Department of Psychology, Tufts University Received 28 September 1989 CANLI, T., R. G, COOK AND K. A. MICZEK. Opiate antagonists enhance the working memory of rats in the radial maze. PHARMACOL BIOCHEM BEHAV 36(3) 521-525, 1990.--Two experiments tested the influence of the opiate antagonists naloxone and naltrexone on the spatial working memory of rats in a 12-arm radial maze. In Experiment 1, ten rats were serially forced to visit six randomly selected arms, then were removed from the maze for delays of either 30, 60, or 240 minutes, and then returned to the maze for a free-choice memory test with all 12 arms available. Five minutes into the delay, rats were injected intraperitoneally (IP) with either physiological saline or naloxone (1 mg/kg). When injected with naloxone the rats revisited forced-choice arms less often than when injected with saline during a subsequent free-choice test. In Experiment 2, twelve rats showed a similar facilitation of working memory when injected with the opiate antagonists naltrexone (0.3 mg/kg) and naloxone (1 mg/kg) in comparison to a saline control condition. These findings demonstrate the beneficial effects that opiate antagonists exert on working memory-based performance in the radial maze. They may also resolve conflicting reports about the influence of opiate antagonists on radial maze performance, by suggesting that the choice of measurement and testing conditions are crucial for detecting these effects in working memory procedures. Spatial working memory Radial arm maze Opiate receptors Naloxone Naltrexone THE opiate antagonist naloxone has been shown to enhance memory in both active and passive avoidance tasks (16,23). The specific cause of this enhancement is difficult to identify, how- ever, because of the multiple effects of opiate antagonists in aversively motivated tasks. For example, research on stress- induced analgesia (13, 17, 20, 21) has shown that an organism will respond with the release of endogenous opiates to both uncondi- tioned and conditioned aversive stimulation. Thus, the effects of opiate antagonists in memory tasks may also reflect contributions of processes related to aversive stimulation, in addition to their presumed capacity to modulate memory. It is therefore important to examine the memory-enhancing effects of opiate antagonists in appetitively motivated tasks also. Thus far, the evidence for the mnemonic role of opiate antagonists in appetitive tasks is mixed (2, 11, 25, 33). The experiments below report that both naloxone and naltrexone increased choice accuracy in a working memory procedure using the appetitively motivated radial maze task. In the radial maze task an animal is placed on an elevated central platform in which a number (e.g., eight) of arms radiate out at equal angles. A small amount of food is available at the end of each arm. The animal is permitted a series of choices among the arms and is thus rewarded with food for the first visit to an arm. Since food is no longer available on previously visited arms, revisits to arms are considered to be "errors." It has been found that rats quickly discriminate and remember which arms they have chosen previously and which still contain food (26). Because it presumably requires the use of spatial information concerning the distribution of food reward, the radial maze has become widely used in studies of the cognitive and neural mechanisms of spatial orientation and memory. Conflicting results have been reported about the influence of opiate antagonists on learning and memory in the radial maze. In one study (11) it was reported that naloxone-treated rats needed significantly less time to relearn a maze placed in a new spatial environment than a saline control group. In contrast, another study (2) failed to show that naloxone and naltrexone had any influence on memory-based choice accuracy in rats tested in eight-arm radial maze using a working memory procedure. One possible reason for this inconsistency may be related to the robust nature of the working memory displayed by rats in the radial maze. It appears that stringent or challenging conditions are often necessary to demonstrate certain treatment effects in this task (5, 22, 28, 31). We decided to reexamine the effects of naloxone on the working memory using a more difficult and possibly more sensitive 12-arm radial maze. EXPERIMENT 1 METHOD Subjects The subjects were 10 male Long-Evans rats (Charles River Laboratories, Wilmington, MA) between 6 and 8 weeks old. They 1Requests for reprints should be addressed to Turhan Canli, Department of Psychology, 2 Hillhouse Ave., Yale University, New Haven, CT 06520. 521