Varied effects of conventional antiepileptics on responding maintained by negative versus positive reinforcement Celeste Roberts a,b , Mark T. Harvey a,b , Michael E. May a,b , Maria G. Valdovinos a,c , Tina G. Patterson b , Maria H. Couppis e , Craig H. Kennedy a,b,d,f, ⁎ a John F. Kennedy Centeron Human Development, Vanderbilt University, Nashville, TN, USA b Department of Special Education, Peabody College of Vanderbilt University, Nashville, TN, USA c Department of Psychology, Drake University, Des Moines, IA, USA d Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA e Department of Psychology, Vanderbilt University, Nashville, TN, USA f Nashville Veterans Administration Medical Center, Nashville, TN, USA Received 1 June 2007; received in revised form 24 October 2007; accepted 1 November 2007 Abstract We analyzed the effects of four conventional antiepileptic drugs (AEDs) – carbamazepine (CBZ), ethosuximide (ETH), phenytoin (PHT), and valproate (VPA) – on operant behavior maintained by negative or positive reinforcement contingencies. Rats were trained to lever press on a free- operant avoidance schedule or variable-interval (VI) schedule of appetitive reinforcement. Dose-effect functions were separately established on each reinforcement contingency for CBZ (12.5–100 mg/kg), ETH (25–200 mg/kg), PHT (12.5–50 mg/kg), and VPA (50–400 mg/kg). CBZ and PHT reduced responding on free-operant avoidance and VI appetitive reinforcement tasks, with positively reinforced behavior reduced at lower drug dosages than negatively reinforced responding. ETH and VPA reduced responding on the VI appetitive reinforcement task, but did not alter behavior maintained on the free-operant avoidance schedule. Our results suggest that conventional AEDs vary in their effect on operant behavior, depending on the type of reinforcement process maintaining responding. © 2007 Published by Elsevier Inc. Keywords: Antiepileptic drugs; Carbamazepine; Ethosuximide; Phenytoin; Valproate; Negative reinforcement; Positive reinforcement; Operant behavior 1. Introduction Problematic behavior, such as aggression or self-injury, is associated with a broad range of neurodevelopmental disabil- ities [1]. People with developmental disabilities (e.g., autism spectrum disorder, fragile-X syndrome) are a clinical population in which problem behavior is of particular concern [2]. Increasingly, psychiatric treatments for behavioral problems in the developmental disabilities have included the use of conventional antiepileptic drugs (AEDs) [3]. This prescription pattern follows a long-term trend in the use of AEDs to treat problem behaviors in other psychiatric populations [4]. Currently, the basis for AED use to treat behavioral problems in the developmental disabilities focuses on the treatment of comorbid psychiatric conditions (e.g., Impulse Control Dis- order) [5]. However, clinical decision-making has yet to take into account the functional properties such behaviors may serve [6]. In the developmental disabilities, most instances of problem behavior function to obtain positive reinforcers and/or avoid negative reinforcers [7,8]. These reinforcement contingencies can maintain a wide variety of behavioral topographies comprising an operant-response class and provides the diag- nostic basis for contemporary behavioral interventions [9,10]. However, yet to be established is how AEDs affect the operant nature of problematic acts, particularly in regard to fundamental behavioral processes such as negative and positive reinforce- ment. Establishing such functional relations may assist in the coordination of behavioral and pharmacological interventions to Physiology & Behavior xx (2007) xxx – xxx PHB-08391; No of Pages 10 ⁎ Corresponding author. John F. Kennedy Center on Human Development, Vanderbilt University, Nashville, TN, USA. Tel.: +1 615 322 8178; fax: +1 615 343 1570. E-mail address: craig.kennedy@vanderbilt.edu (C.H. Kennedy). 0031-9384/$ - see front matter © 2007 Published by Elsevier Inc. doi:10.1016/j.physbeh.2007.11.001 ARTICLE IN PRESS Please cite this article as: Roberts C, et al, Varied effects of conventional antiepileptics on responding maintained by negative versus positive reinforcement, Physiol Behav (2007), doi:10.1016/j.physbeh.2007.11.001