l-DOPA improves odor discrimination learning in rats Michelle Pavlis, Casara Feretti, Alan Levy, Nita Gupta, Christiane Linster * Department of Neurobiology and Behavior Mudd Hall, Cornell University, Ithaca, NY 14853, United States Received 6 May 2005; received in revised form 7 September 2005; accepted 7 September 2005 Abstract Using a forced-choice odor discrimination task in rats, we show here that intraperitoneal injections of l-DOPA improve rats’ odor discrimination performance in comparison to control rats injected with saline. Although the exact mechanism of l-DOPA and potential action on dopamine receptors remains unclear, the present results indicate that rats injected with the 20 – 50 mg/kg of l-DOPA performed significantly better in an odor discrimination task than did control rats. In addition, we observed a significant correlation between the concentration of l-DOPA and odor discrimination performance. D 2005 Elsevier Inc. All rights reserved. Keywords: l-DOPA; Olfaction; Rats; Discrimination 1. Introduction To date, several lines of evidence suggest that olfactory perception is modulated by dopaminergic activity. For example, i.p. injections of the D2 dopamine receptor antagonist spiperone mimic the electrophysiological effects of olfactory deprivation in rats [1], while injections of the D2 agonist quinpirole both produce a dose-dependent decrease in odor detection performance in rats [2] and nearly eliminate the activity-dependent accumulation of 2-deoxyglucose in the olfactory bulb elicited by odor stimulation [3]. Dopaminergic modulation is also involved in some forms of olfactory learning [4–8]. In addition, our laboratory has shown that the modulation of D1 and D2 dopaminergic receptors has opposing effects on rats’ odor discrimination capabilities: injection of either the D1 agonist SKF 38393 or the D2 antagonist spiperone facilitated odor discrimination, whereas both the D1 antagonist SCH 23390 and the D2 agonist quinpirole significantly impaired the discrimination odorants in that study [9]. Here, we show that a non-specific increase of dopaminer- gic modulation, induced by injection with the dopamine precursor l-3,4-dihydroxyphenylalanine (l-DOPA) improves rats’ olfactory discrimination capabilities. Using a forced- choice odor discrimination task, we demonstrate that there is a significant correlation between the concentration of the dopamine increasing drug and the rats’ performance. 2. Methods The behavioral methods were similar to those previously used in our laboratory to test olfactory discrimination in rats using a naturalistic task and have been described in detail elsewhere [9,10,11]. 2.1. Subjects Thirty-two male Sprague – Dawley Rats (Charles River Laboratories, Wilmington, MA), weighing between 250 g and 400 g, served as subjects for the discrimination experiments. The rats were maintained on a 12:12-h light– dark cycle in an environmentally controlled room and housed in pairs. Although water was continuously available throughout behavioral testing, a food-deprivation schedule was followed to maintain the rats at approximately 85–95% of their ad libitum body weight over the experimental period. Daily discrimination experiments were conducted in the afternoon (1300 – 1700). All procedures were performed 0031-9384/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.physbeh.2005.09.011 * Corresponding author. Tel.: +1 607 2544331. E-mail address: CL243@cornell.edu (C. Linster). Physiology & Behavior 87 (2006) 109 – 113