ELSEVIER Neuroscience Letters 211 (1996) 73-76 Conditioned changes in nucleus accumbens dopamine signal established by intravenous cocaine in rats Eugene A. Kiyatkinq*, Elliot A. Steimb aDrpartment of Psychiatry, Medical College of Wisconsin, Milwaukee, WI 53226, USA bDepartment of Pharmacology, Medical College of Wisconsin, Milwaukee, WI 53226, USA Received 19 March 1996; revised version received 25 April 1996; accepted 9 May 1996 Abstract To explore the role of cocaine-induced conditioning in the regulation of mesolimbic dopamine (DA) activity, high-speed chronoam- perometry with Nafion-coated carbon fiber electrodes was used to measure changes in nucleus accumbens (NAc) DA-dependent signal induced by a light stimulus previously paired and not paired with intravenous cocaine (0.85 mgkg per injection), and cocaine injec- tions paired and not paired with light. A small phasic DA signal increase was found after light presentation in drug-naive rats, whereas greater and longer signal increases were induced by the same light after it had been repeatedly paired with cocaine. The DA signal changes associated with repeated cocaine injections paired with light differed from those induced by cocaine alone and occurring dur- ing drug self-administrations. These data suggest that cocaine-related sensory cues, acting alone, may induce a conditioned mesolimbic DA activation, and, acting in the presence of the drug, may significantly modify the DA response to the drug. Keywords: Dopamine; Conditioning; Electrochemistry; Behavioral sensitization; Cocaine craving; Drug-taking behavior Cocaine is a powerful drug reinforcer [4,1.5], and much evidence suggests that Pavlovian conditioning plays an important role in the development of conditioned place preferences [8,20], beh.avioral sensitization [8,9,20] and operant self-administration (SA) behavior [23] quickly established by cocaine. Since the mesolimbic dopamine (DA) system plays an (essential role in the organization and regulation of goal-directed behavior [4,24], and co- caine is a potent inhibitlor of DA reuptake [ 1,7], changes in mesolimbic DA activity induced by cocaine and stimuli associated with its administration may be involved in mediating the enhanced behavioral responses to repeated drug. Increases in nucleus accumbens (NAc) DA res- ponses found during repeated cocaine injections using both microdialysis [9] and voltammetry [lo] appear con- sistent with this point of view. Mechanisms of condition- ing contribute to changes in mesolimbic DA transmission occurring during cocaine SA behavior [6,13]. NAc DA signal was found to gradually increase in trained rats after * Corresponding author. Present address: Program in Neural Sciences, Indiana University, Psychology Building, Bloomington, IN 47405 1301, USA; Tel.: + 1 812 8555537; fax: + 1 812 8554520. presentation of a light cue previously paired with cocaine SAs. Since, in these experiments, light also triggered drug-taking behavior, it is likely that behavior may have contributed to the observed DA signal increase. To fur- ther explore the phenomenon of conditioned activation of the mesolimbic DA system established by cocaine, high- speed chronoamperometry with DA-selective carbon fiber electrodes was used to estimate changes in NAc extracel- lular DA levels following the presentation of a light stimulus that was either paired or not paired with cocaine and during repeated cocaine administration either alone or when paired with light. Experiments were performed on male Long-Evans rats prepared with a DA-sensitive electrochemical electrode aimed at the medial sector of NAc (1.6 mm anterior to bregma, 1.6 mm lateral to midline and 7.2-7.4 mm ven- tral from the surface of the cortex), and an intravenous (i.v.) jugular catheter, as previously described [ 131. These electrodes exhibit high DA sensitivity (detection thresh- old 540 nM for one test at a 5 s integration rate), a linear response to increasing DA concentration, and high selec- tivity to DA against ascorbic acid (800-1OOO:l) and 3,4- dihydroxyphenylacetic acid (DOPAC) (400-500: 1). 0304-3940/96/$12.00 0 1996 Elsevier Science Ireland Ltd. All rights reserved PII SO304-3940(96)127:11-O