PharmacologyBiochemistry & Behavior, Vol. 25, pp. 269--276,1986.©AnkhoInternational Inc. Printedin the U.S.A. 0091-3057/86$3.00 + .00 Motor Activity Changes and Conditioned Taste Aversions Induced by Administration of Scopolamine in Rats: Role of the Area Postrema KLAUS-PETER OSSENKOPP, CATHERINE SUTHERLAND AND RICKI L. LADOWSKY Department of Psychology, University of Western Ontario, London, Ontario, Canada, N6A 5C2 OSSENKOPP, K.-P., C. SUTHERLAND AND R. L. LADOWSKY. Motor activity changes and conditioned taste aversions induced by administration of scopolamine in rats: Role of the area postrema. PHARMACOL BIOCHEM BEHAV 25(1) 269--276, 1986.--Three experiments examined the effects of centrally and peripherally acting scopolamine (scopolamine hydrochloride-SHC) or only peripherally acting scopolamine (scopolamine methyl nitrate-SMN), on motor activity levels and the ability of these agents to induce taste aversions. In Experiment 1 rats were injected with isotonic saline, 1 mg/kg SHC, or 1 mg/kg SMN. SHC produced significant increases in stabilimeter activity (p <0.025) and in rearing response frequency (p<0.01), whereas SMN resulted in significantly less activity (,o<0.025). Both agents induced strong conditioned taste aversions to saccharin (p<0.01). Experiment 2 examined the role of the area postrema in mediating these drug induced behavioral changes. Sham lesioned and area postrema lesioned rats were given saline, SHC or SMN (1 mg/kg for both drugs) and examined for changes in activity, rearing response frequency and induction of taste aversions to saccharin. SHC again produced significant increases in activity (p <0.01) and in rearing responses (p <0.01), whereas SMN produced decrements in activity (p <0.05). However, the brain lesion did not consistently alter the effects of these drugs on activity but it did reduce the amount of the decrement observed in rearing responses in SMN treated rats. The brain lesion also altered the ability of the drugs to induce taste aversions. Both SMN and SHC produced strong taste aversions in the sham lesioned rats (/7<0.01) but no significant aversions were observed in the area postrema lesioned rats. Experiment 3 examined the ability of the brain lesion to alter the effects of SMN by using a within groups design. Area postrema lesions were found to attenuate but not abolish, the inhibitory effects of SMN on both activity levels and rearing responses (o<0.03). The results of these experiments suggest that in the absence of the chemically-sensitive area postrema both SMN and SHC fail to induce taste aversions and the inhibitory effect of SMN on spontaneous activity is attenuated. Area postrema Conditioned taste aversions Scopolamine hydrochloride Brain lesions Hyperactivity Behavioral depression Rats Scopolamine methyl nitrate IN rodents anticholinergics such as scopolamine and at- ropine increase locomotor activity when they act on the cen- tral nervous system [1, 16--18, 30, 32, 34], however, quaternary anticholinergics, which do not cross the blood- brain-barrier are reported to have either no significant effect on motor activity (e.g., [13, 16, 32]) or to inhibit activity levels [17]. Scopolamine is also a highly effective agent for induction of conditioned taste aversions (CTA). Strong avoidance conditioning of a novel taste can be produced in rats by pairing ingestion of the novel tasting substance with exposure to a toxic agent such as lithium [14,19] or to ioniz- ing radiation [31], and the suggestion has been made that it is the illness-inducing properties of these treatments which make them such effective agents in producing CTA [9,10]. Both centrally and peripherally acting scopolamine can produce robust CTA in rats [2,3] and several experiments have shown that the peripherally acting scopolamine acts on the area postrema (AP) in the fourth ventricle to induce this type of avoidance behavior [3,20]. The AP is a circumventricular structure containing cen- tral chemoreceptors, which when stimulated, can initiate an emetic response in animals capable of vomiting [4--6]. An analagous role for the AP in detection of toxic agents in non-emetic mammals, such as rats, has been shown in exper- iments on rats with AP lesions. Destruction of the AP results in the absence of CTA normally induced by scopolamine methyl nitrate [3,20], lithium [14, 26, 29] or exposure to ionizing radiation [21, 23, 26, 27]. The AP also seems to mediate the depression in activity seen in rats treated with lithium chloride [14]. Rats with AP lesions no longer dis- played the reductions in activity shown by the sham lesioned animals after administration of the lithium. Ladowsky and Ossenkopp [14] suggested that the depression in activity normally seen after acute administration of lithium may re- sult at least partially from malaise or nausea and that stimu- lation of the AP by the lithium may be a sufficient condition to induce such malaise. If both the CTA and the depression in activity resulted from activation of the AP by the lithium, 269