Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr The Effect of Methylphenidate on the Microstructure of Schedule-Induced Polydipsia in an animal model of ADHD ☆ Javier Íbias a,c , Carter W. Daniels b , Miguel Miguéns c , Ricardo Pellón c , Federico Sanabria b, ⁎ a Western University of Health Sciences, Pomona, CA, USA b Arizona State University, Tempe, AZ, USA c Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain ARTICLE INFO Keywords: Schedule-induced polydipsia Methylphenidate Attention-deficit hyperactivity disorder Bouts Spontaneously hypertensive rat Wistar Kyoto rats ABSTRACT Schedule-induced polydipsia (SIP) was established in spontaneously hypertensive rats (SHR), Wistar Kyoto rats (WKY), and Wistar rats, using a multiple fixed-time (FT) schedule of food delivery, with 30- and 90-s compo- nents. Thereafter, animals were exposed to methylphenidate (MPH; 2.5 mg/kg/d) for six consecutive SIP ses- sions. A test to assess possible sensitization effects was also conducted four days after termination of the drug treatment. At baseline, FT 90-s produced longer and more frequent drinking episodes in SHR than in WKY. An analysis of the distribution of inter-lick intervals revealed that drinking was organized in bouts, which were shorter in SHR than in WKY. Across strains and schedules, MPH shifted drinking episodes towards the beginning of inter-food intervals, which may reflect a stimulant effect on SIP. MPH transiently reduced the frequency of drinking episodes in WKY in FT 30-s, and more permanently reduced the frequency of licking bouts in Wistar rats. MPH also increased the length of licking bouts in Wistar rats. Overall, SHR displayed a hyperactive-like pattern of drinking (frequent but short bouts), which 2.5 mg/kg MPH appears to reduce in WKY and Wistar but not in SHR rats. It appears that therapeutic effects of MPH on hyperactive-like SIP require higher doses in SHR relative to control strains. 1. Introduction The most common symptoms observed in the hyperactive/impulsive subtype of attention deficit hyperactivity disorder (ADHD) are hyper- activity and an increased sensitivity to the delay of reinforcement [1,2]. The chronic administration of stimulants attenuates these symptoms [3]. In particular, methylphenidate (MPH), a norepinephrine-dopamine reuptake inhibitor, is the most common treatment to control symptoms of ADHD [4–6]. The spontaneously hypertensive rat (SHR) is a validated animal model of ADHD [7–9]. It displays most of the symptoms of ADHD, in- cluding hyperactivity [10–12], sensitivity to delay of reinforcement [13], and inattention, although inattention is observed only when re- inforcers are delayed [14]. Hyperactivity appears to facilitate learning and persistence in SHR rats, which in turn facilitate the acquisition of new behaviors [15]. In fact, SHR hyperactivity is particularly notice- able in weakly reinforced responses [10]. Nonetheless, behavioral and pharmacological evidence suggests that the SHR model does not mimic the full spectrum of symptoms associated with ADHD [11,14,16]. SHR rats display an enhanced acquisition of schedule-induced polydipsia (SIP; [17,18]). SIP is the excessive drinking observed in animals that are slightly food deprived, when they have free access to water and periodic access to small quantities of food [19]. SIP is ob- served even if there is no arranged contingency between drinking and the delivery of the food [20]. Of importance to this study, SIP is con- sidered a behavioral model of compulsive behavior [21–23]. SIP emerges with varied strength under Pavlovian contingencies [24], but their rate of occurrence and their distribution seem to be governed by operant rules underlying both their development and maintenance [25]. The drinking behavior of SHR, when access to food is periodic, is consistent with the instrumental basis of SIP. When comparing SHR against control strains, differences in the distribution of inter-lick in- tervals (ILIs) during SIP are similar to differences in the distribution of instrumental inter-response times [10,26]. Previous work indicates that ILIs during SIP are well described by the Biexponential Refractory Model (BERM) of free-operant perfor- mance [27,28]. According to this model, subjects fluctuate in and out of drinking bouts such that three parameters characterize the distribution http://dx.doi.org/10.1016/j.bbr.2017.06.048 Received 6 May 2017; Received in revised form 23 June 2017; Accepted 29 June 2017 ☆ Research was supported by grant PSI2011-29399, and preparation of manuscript by grant PSI2016-80082-P, both from Ministerio de Economía y Competitividad, Secretaría de Estado de Investigación, Desarrollo e Innovación (Government of Spain). ⁎ Corresponding author. E-mail address: federico.sanabria@asu.edu (F. Sanabria). Behavioural Brain Research 333 (2017) 211–217 Available online 30 June 2017 0166-4328/ © 2017 Elsevier B.V. All rights reserved. MARK