Ike dela Peña1, Edson Luck Gonzales2, June Bryan de la Peña1, Bung-Nyun Kim3, Doug Hyun Han4, Chan Young Shin2, Jae Hoon Cheong5. 1. Uimyung Research Institute for Neuroscience, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815 Nowon-gu, Seoul 139-742, Republic of Korea. 2. Department of Neuroscience, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea. 3. Division of Child and Adolescent Psychiatry, Clinical Research Institute, Seoul National University Hospital, 28 Yungundong, Chongrogu, Seoul 110-744, Republic of Korea. 4. Department of Psychiatry, Chung-Ang University Medical School, 102 Heukseok-ro, Dongjak-gu, Seoul 156-755, Republic of Korea. 5. Uimyung Research Institute for Neuroscience, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815 Nowon-gu, Seoul 139-742, Republic of Korea. Electronic address: cheongjh@syu.ac.kr.
Abstract
BACKGROUND: High novelty seeking has been assumed to predict vulnerability to use addictive drugs. Notably, it is also a symptom associated with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to identify whether spontaneously hypertensive rats (SHRs), putative animal models of ADHD, display individual differences in novelty-seeking behavior, and whether high novelty-seeking SHRs show enhanced sensitivity to the reinforcing effect of methylphenidate, the most commonly prescribed stimulant ADHD medication. METHODS: First, we established that SHRs show higher levels of novelty-seeking behavior than their normotensive control strain, Wistar Kyoto (WKY) rats. Novelty seeking was measured in two tests: open field test in a novel test arena, and novel object preference tests. Thereafter, SHRs were classified into high responders (HR) or low responders (LR), high novelty-preferring (HNP) or low novelty-preferring (LNP) rats, based on individual scores in the two behavioral assays. Methylphenidate self-administration was assessed thereafter. RESULTS: SHRs showed higher levels of novelty-seeking behavior than WKY rats. HR/LR and HNP/LNP subgroups were identified. HR and LR rats showed comparable rates of methylphenidate self-administration. However, HNP SHRs worked more for methylphenidate infusions than their LNP counterparts. CONCLUSIONS: We showed some evidence on inter-individual variations in novelty seeking in SHRs. Importantly, we demonstrated enhanced sensitivity of HNP SHRs to the reinforcing effect of methylphenidate, indicating a "drug-vulnerable" SHR subpopulation. These findings are important as they may provide basis for a potential screening tool to identify a subset of ADHD patients (i.e. high novelty seekers) who may be at risk for misusing/abusing methylphenidate.
BACKGROUND: High novelty seeking has been assumed to predict vulnerability to use addictive drugs. Notably, it is also a symptom associated with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to identify whether spontaneously hypertensiverats (SHRs), putative animal models of ADHD, display individual differences in novelty-seeking behavior, and whether high novelty-seeking SHRs show enhanced sensitivity to the reinforcing effect of methylphenidate, the most commonly prescribed stimulant ADHD medication. METHODS: First, we established that SHRs show higher levels of novelty-seeking behavior than their normotensive control strain, Wistar Kyoto (WKY) rats. Novelty seeking was measured in two tests: open field test in a novel test arena, and novel object preference tests. Thereafter, SHRs were classified into high responders (HR) or low responders (LR), high novelty-preferring (HNP) or low novelty-preferring (LNP) rats, based on individual scores in the two behavioral assays. Methylphenidate self-administration was assessed thereafter. RESULTS: SHRs showed higher levels of novelty-seeking behavior than WKY rats. HR/LR and HNP/LNP subgroups were identified. HR and LR rats showed comparable rates of methylphenidate self-administration. However, HNP SHRs worked more for methylphenidate infusions than their LNP counterparts. CONCLUSIONS: We showed some evidence on inter-individual variations in novelty seeking in SHRs. Importantly, we demonstrated enhanced sensitivity of HNP SHRs to the reinforcing effect of methylphenidate, indicating a "drug-vulnerable" SHR subpopulation. These findings are important as they may provide basis for a potential screening tool to identify a subset of ADHDpatients (i.e. high novelty seekers) who may be at risk for misusing/abusing methylphenidate.
Authors: M Carmen Arenas; María A Aguilar; Sandra Montagud-Romero; Ana Mateos-García; Concepción I Navarro-Francés; José Miñarro; Marta Rodríguez-Arias Journal: Curr Neuropharmacol Date: 2016 Impact factor: 7.363