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Neurobiology of Learning and Memory 86 (2006) 305–310

Post-training amphetamine administration enhances memory consolidation in appetitive Pavlovian conditioning: Implications for drug addiction
Nicholas W. Simon a, Barry Setlow a,b,¤

Department of Psychology, Texas A&M University, College Station, TX 77843-4235, USA b Faculty of Neuroscience, Texas A&MUniversity, College Station, TX 77843-4235, USA Received 9 March 2006; revised 19 April 2006; accepted 20 April 2006 Available online 5 June 2006

Abstract It has been suggested that some of the addictive potential of psychostimulant drugs of abuse such as amphetamine may result from their ability to enhance memory for drug-related experiences through actions on memory consolidation. Thisexperiment examined whether amphetamine can speciWcally enhance consolidation of memory for a Pavlovian association between a neutral conditioned stimulus (CS—a light) and a rewarding unconditioned stimulus (US—food), as Pavlovian conditioning of this sort plays a major role in drug addiction. Male Long-Evans rats were given six training sessions consisting of 8 CS presentations followed by delivery of thefood into a recessed food cup. After the 1st, 3rd, and 5th session, rats received subcutaneous injections of amphetamine (1.0 or 2.0 mg/kg) or saline vehicle immediately following training. Conditioned responding was assessed using the percentage of time rats spent in the food cup during the CS relative to a pre-CS baseline period. Both amphetamine-treated groups showed signiWcantly moreselective conditioned responding than saline controls. In a control experiment, there were no diVerences among groups given saline, 1.0 or 2.0 mg/kg amphetamine 2 h post-training, suggesting that immediate post-training amphetamine enhanced performance speciWcally through actions on memory consolidation rather than through non-mnemonic processes. This procedure modeled Pavlovian learning involved in drugaddiction, in which the emotional valence of a drug reward is transferred to neutral drug-predictive stimuli such as drug paraphernalia. These data suggest that amphetamine may contribute to its addictive potential through actions speciWcally on memory consolidation. © 2006 Elsevier Inc. All rights reserved.
Keywords: Pavlovian conditioning; Amphetamine; Drug addiction; Memory consolidation;Learning; Post-training; Classical conditioning

1. Introduction Pavlovian conditioning plays a signiWcant role in drug addiction. Cues that are consistently predictive of drug intake (such as drug paraphernalia or drug-taking contexts) can become associated with rewarding properties of the drug itself. This associative learning results in retrieval of drug-related experiences and aVect uponencounters with these cues, which may lead to craving and relapse. The strong inXuence of Pavlovian conditioning provides an


Corresponding author. Fax: +1 979 845 4727. E-mail address: (B. Setlow).

explanation for the diYculty drug users have with maintaining drug abstinence long after physical dependence is no longer evident (Childress et al., 1999; Ciccocioppo,Martin-Fardon, & Weiss, 2004; Everitt, Dickinson, & Robbins, 2001; Shaham, Shalev, Lu, de Wit, & Stewart, 2003). It has been proposed that psychostimulant drugs (such as amphetamine and cocaine) may actually strengthen the inXuence of Pavlovian conditioning over drug addiction through their actions on memory consolidation processes (White, 1996). Psychostimulants can enhance memory for previously learnedinformation (for review, see McGaugh, 1966; McGaugh, 2000), and this drug-induced memory enhancement process would be expected to strengthen associations between the drug and the cues preceding it. Enhanced

1074-7427/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.nlm.2006.04.005


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