Cocaine facilitates craving via an action on sensory processing Paul G. Overton a, *, Ian M. Devonshire b a Department of Psychology, University of Sheffield, Western Bank, Sheffield, S10 2TP, UK b Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK Received 26 February 2008; received in revised form 18 March 2008; accepted 25 March 2008 KEYWORDS Psychostimulants; Addiction; Attention; Conditioning; Cue-induced craving Abstract Sensory systems play an important role in cocaine addiction, perhaps most clearly demonstrated when stimuli (‘cues’) associated via classical conditioning with the effects of the drug, trigger craving and relapse. It has been shown in previous studies that administration of cocaine can enhance evoked responses in the primary sensory cortex of experimental animals. Given that the speed of learning in classical conditioning is affected by the intensity of the conditioned stimulus (CS), and that cocaine enhances the neural representation of sensory stimuli in the primary sensory cortex in a manner similar to an increase in intensity, we hypothesise that cue-induced craving in human addicts is facilitated by the drug. In short, co- caine speeds the process that leads to craving. This hypothesis is supported by the fact that cocaine enhances sensory responses in humans and leads to an improvement in attention (the putative intermediary between enhanced sensory responses and facilitated learning). Furthermore, cocaine affects neural loci which are known to play a role in learning and facilitates classical conditioning when present during acquisition. In addition, related drugs like d-amphetamine and ecstasy (which themselves produce craving) affect sensory processing and attention, and in the case of d-amphetamine facilitate human learning. It is therefore possible that cocaine itself plays a e previously under-appreciated e role in the formation of associations between drug and drug-related environmental cues by enhancing primary sensory responses. A corollary of this is that, as with other intense CSs, the established asso- ciation may be particularly resistant to extinction, potentially explaining why cues continue to elicit craving months or even years after the last cocaine use. ª 2008 Elsevier Ltd. All rights reserved. Craving, cocaine and sensitisation Craving, a ‘hunger for drugs’ [1], is one of the cardinal fea- tures of drug dependence in humans, and its importance in perpetuating the consumption of a range of drugs of abuse has been widely acknowledged (e.g. [2]). In relation to * Corresponding author. Tel.: þ44 (0)114 222 6624; fax: þ44 (0)114 276 6515. E-mail address: p.g.overton@sheffield.ac.uk (P.G. Overton). 1756-2392/$ - see front matter ª 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.bihy.2008.03.002 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/bihy Bioscience Hypotheses (2008) 1, 70e77