Psychopharmacology (2012) 220:771–785 DOI 10.1007/s00213-011-2525-8 ORIGINAL INVESTIGATION Seeking–taking chain schedules of cocaine and sucrose self-administration: effects of reward size, reward omission, and α-flupenthixol M. M. J. Veeneman & M. van Ast & M. H. Broekhoven & J. H. W. Limpens & L. J. M. J. Vanderschuren Received: 19 October 2010 / Accepted: 27 September 2011 / Published online: 12 October 2011 # The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Rationale In heterogeneous seeking–taking (ST) chain schedules of self-administration, seeking rewards and taking rewards are distinct actions, giving animals explicit control over their intake of the reward. However, the neurobehavioral characteristics of ST chain schedules are relatively unexplored. Objectives This study was made to evaluate two variants of ST chain schedules of self-administration to measure seeking and taking of sucrose and cocaine in rats. Methods Rats had to respond on one lever (seeking lever) under a random interval (RI) or under a progressive ratio (PR) schedule, to gain access to a second lever (taking lever), responding on which under a fixed-ratio 1 (FR-1) schedule of reinforcement delivered the reward. We assessed the effects of reward size, reward omission, and administration of the dopamine receptor antagonist α- flupenthixol. The effects of α-flupenthixol on responding for cocaine or sucrose under an FR-1 schedule of reinforcement were also assessed. Results Cocaine seeking under both schedules was reduced by decreasing reward size, reward omission, and α-flupenthixol treatment. Cocaine taking was decreased M. M. J. Veeneman : M. van Ast : M. H. Broekhoven : J. H. W. Limpens : L. J. M. J. Vanderschuren (*) Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands e-mail: l.j.m.j.vanderschuren@umcutrecht.nl L. J. M. J. Vanderschuren Division of Behavioural Neuroscience, Department of Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands by α-flupenthixol treatment and reward omission, but not by altering reward size. Sucrose seeking was not affected by reward size, but was reduced by α-flupenthixol and reward omission. Sucrose taking was diminished by reward omission only. α-Flupenthixol increased cocaine but not sucrose intake under an FR-1 schedule of reinforcement. Conclusions Both ST(PR) and ST(RI) schedules can be used to assess seeking and taking of sucrose and cocaine. Dopaminergic neurotransmission mediates the positive subjective properties of cocaine but not sucrose and the motivational properties of both sucrose and cocaine. Keywords Addiction . Motivation . Cocaine . Dopamine . Food Introduction Drugs are initially used because of their pleasurable subjective effects. However, casual drug use can progress into inappropriate and excessive use, finally culminating in drug addiction, characterized by loss of control over drug intake. One of the mechanisms underlying the development of addiction is that drugs of abuse usurp neurobehavioral processes that mediate the motivational properties of rewards (Robinson and Berridge 1993; Vanderschuren and Everitt 2005; Koob and Volkow 2010). Increasing our understanding of the motivational processes that govern drug use and drug addiction may aid the development of a successful pharmacotherapy for addiction. To accomplish this, it is essential to have an animal model that emulates drug seeking and taking as it occurs in humans and in which we can reliably measure the motivation for drugs. Progressive ratio (PR) schedules of reinforcement are the most widely used self-administration schedules to study the