Research Report Methylphenidate response in prenatal cocaine-exposed rats: A behavioral and brain functional study Annelyn Torres-Reveron a,b,1 , Jeremy Weedon c , Diana L. Dow-Edwards a,b, ⁎ a Program in Neural and Behavioral Sciences, State University of New York, Brooklyn, New York, USA b Department of Physiology and Pharmacology, State University of New York, Brooklyn, New York, USA c Scientific Computing Center SUNY Health Sciences Center at Brooklyn, Brooklyn, New York, USA ARTICLE INFO ABSTRACT Article history: Accepted 31 March 2010 Available online 9 April 2010 Prenatal cocaine exposure is associated with abnormal arousal and attention in children. Since methylphenidate (MPD) is widely used to treat attention disorders, we wanted to determine whether prenatal cocaine exposure affects brain function in response to MPD as measured by glucose metabolism in a rodent model. Pregnant rats received 60 mg/kg cocaine or vehicle from gestational days 8–22 by intragastric intubation. On a single day between postnatal days 41–45, offspring received 10 mg/kg i.p. of MPD or saline. After 15 min, the quantified 2-deoxyglucose (2DG) method was carried out in freely behaving animals. Seventy nine brain regions were assessed but we focused on functional units such as the mesolimbic and motor circuits which were analyzed using mixed linear models. MPD increased glucose metabolism in most brain regions from 15% to 30% over saline regardless of the prenatal treatment. Prenatal cocaine produced insignificant effects on the rates of brain glucose metabolism overall but produced a reduced response to MPD in the nucleus accumbens in a rostral/caudal gradient compared to control. In addition, correlations of rates of metabolism in the mesolimbic and nigrostriatal systems with the amount of MPD- induced behavior (stereotypy and locomotion) show that prenatal cocaine alters the relationship between regional metabolism and behavior in sex-specific ways. In summary, prenatal cocaine has minimal effects on brain metabolic activity even under drug challenge conditions but has a major impact on the relationship between brain metabolism and behavior. © 2010 Published by Elsevier B.V. Keywords: Prenatal cocaine Brain metabolism Methylphenidate Adolescence Sex difference 1. Introduction Recent clinical and animal studies are converging on a description of attention problems in individuals that have been exposed to cocaine in utero (Noland et al., 2005; Savage et al., 2005; Gendle et al., 2004; Bandstra et al., 2001; Garavan et al., 2000). Both clinical trials and animal experiments have demonstrated that prenatal cocaine exposure produces BRAIN RESEARCH 1337 (2010) 74 – 84 ⁎ Corresponding author. 450 Clarkson Avenue, Box 29, Brooklyn, NY 11203, USA. Fax: +1 718 270 2241. E-mail addresses: at583@nova.edu (A. Torres-Reveron), diana.dow-edwards@downstate.edu (D.L. Dow-Edwards). Abbreviations: MPD, methylphenidate; 2DG, 2-deoxyglucose; PND, postnatal day; G, gestational day; ADHD, attention deficit hyperactivity disorder; MLM, mixed linear model; SEM, standard error of the mean 1 Current address: Nova Southeastern University, College of Pharmacy, 2250 Ave. Las Americas, Suite 607, Ponce, Puerto Rico, 00717. Fax: +1 787 651 2009. 0006-8993/$ – see front matter © 2010 Published by Elsevier B.V. doi:10.1016/j.brainres.2010.03.112 available at www.sciencedirect.com www.elsevier.com/locate/brainres