Original article 21 Chronic methylphenidate treatment during adolescence increases anxiety-related behaviors and ethanol drinking in adult spontaneously hypertensive rats Leandro F. Vendruscolo a, *, Geison S. Izı ´dio b, *, Reinaldo N. Takahashi a and Andre ´ Ramos b Methylphenidate (MPD) is the most widely used drug in the treatment of attention-deficit hyperactivity disorder (ADHD), the symptoms of which can persist into adolescence and adulthood. The cooccurrence of other psychiatric disorders, such as anxiety and alcoholism, in adults with ADHD is very common, but its etiology remains largely unknown. This study examined the effects of chronic MPD treatment during adolescence on emotional and consummatory behaviors in adult spontaneously hypertensive rats (SHRs), often proposed as an animal model of ADHD. Adolescent SHRs of both sexes were given chronic treatment with MPD (2 mg/kg intraperitoneally; twice daily for 16 days) or vehicle and were subsequently tested in adulthood. The tests used were the open-field and the elevated plus-maze, thought to measure locomotor and emotionality-related behaviors, and a protocol of ethanol consumption. MPD elicited anxious-like behavior in the open-field (but not in the elevated plus-maze) regardless of sex, and enhanced ethanol intake in females. These findings suggest that MPD treatment during adolescence induces persistent changes on emotionality and ethanol consumption in SHRs, but these effects depend on the sex and behavioral test used. Potential clinical implications of these findings are discussed. Behavioural Pharmacology 19:21–27  c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins. Behavioural Pharmacology 2008, 19:21–27 Keywords: alcoholism, anxiety disorders, drug addiction, elevated plus-maze, sex differences, open-field, spontaneously hypertensive rat, two-bottle voluntary ethanol drinking a Departamento de Farmacologia and b Departamento de Biologia Celular, Embriologia e Gene ´ tica, Centro de Cie ˆ ncias Biolo ´ gicas, Universidade Federal de Santa Catarina, Floriano ´ polis, Santa Catarina, Brazil Correspondence to Dr Leandro F. Vendruscolo, Laborato ´ rio de Psicofarmacologia I, Departamento de Farmacologia, CCB, Universidade Federal de Santa Catarina, 88.040-900, Floriano ´ polis, Santa Catarina, Brazil E-mail: vendruscolo@hotmail.com *Leandro F. Vendruscolo and Geison S. Izı ´dio contributed equally to this work. Received 19 May 2007 Accepted as revised 13 September 2007 Introduction Attention-deficit hyperactivity disorder (ADHD), one of the most common childhood neuropsychiatric disorders, includes behavioral and cognitive symptoms, such as inattention and impulsivity/hyperactivity. In more than 50% of children with ADHD, the symptoms persist into adolescence and adulthood (Murphy and Barkley, 1996; Goldman et al., 1998). It is now estimated that 4% of adults suffer from ADHD (Faraone and Biederman, 2005; Kessler et al., 2006). Moreover, there has been an increasing recognition of the cooccurrence of ADHD with other psychiatric disorders, notably mood disorders, anxiety disorders and drug addiction (Biederman et al., 1994; Biederman, 2005; Wilens et al., 2005; Fischer et al., 2007). The presence of more than one cooccurring psychiatric disorder with ADHD is also common. For example, individuals with ADHD and substance use disorders present higher rates of anxiety disorders than individuals with either ADHD or substance use disorder alone (Wilens et al., 2005). The identification of the neurobiological mechanisms underlying ADHD with comorbidity is necessary as this condition may further complicate the diagnosis and treatment of the individuals (Wilens et al., 2005). Methylphenidate (MPD), also known as Ritalin, is the most widely used drug in the treatment of ADHD (see, for review, Leonard et al., 2004). MPD is a piperidine derivative known to block dopamine (DA) uptake by brain DA transporters (Gatley et al., 1996) in a similar way to potent psychostimulants such as cocaine and amphe- tamine. MPD is very effective in treating ADHD; however, its adverse effects remain controversial. Although there is evidence showing that therapeutic treatment of ADHD with MPD increases the risk of drug addiction (Lambert and Hartsough, 1998), other studies have actually reported that this treatment reduces the risk of substance abuse disorders (Biederman et al., 1999). The role of MPD treatment in other cooccurring psychiatric disorders remains to be established. Studies in adult rats that had been exposed to chronic MPD during development are inconsistent (see, for review, Kuczenski and Segal, 2005). For example, 0955-8810  c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.