title: The effects of atomoxetine and methylphenidate on the prepulse inhibition of the acoustic startle response in mice.
abstract: Atomoxetine (ATM) and methylphenidate (MPD) have been used for the treatment of attention deficit hyperactivity disorder (ADHD). ATM is a selective norepinephrine reuptake inhibitor, whereas MPD is a psychostimulant and acts as a norepinephrine and dopamine reuptake inhibitor. In the present study, we investigated the effects of ATM (1, 3 or 10mg/kg) and MPD (5, 10 or 20mg/kg) on pharmacological mouse models of sensorimotor gating measured by prepulse inhibition (PPI) using the acoustic startle response test. MK-801, a non-competitive N-methyl-d-aspartate receptor antagonist, or apomorphine, a non-competitive dopamine receptor agonist, was used to induce PPI deficits. ATM (3 or 10mg/kg, s.c.) significantly attenuated the MK-801-, but not apomorphine-, induced PPI deficits. In contrast to ATM, MPD did not reverse the PPI deficits induced by either MK-801 or apomorphine. Immunostaining revealed that the number of c-Fos-immunopositive cells was increased in the nucleus accumbens following MK-801 treatment, and this was reversed by the administration of ATM (3mg/kg), but not MPD (10mg/kg). However, neither ATM nor MPD reversed the increased number of c-Fos-immunopositive cells in the nucleus accumbens following apomorphine treatment. These results suggest that the attenuating effect of ATM on the increased c-Fos immunoreactivity in the nucleus accumbens induced by MK-801 may be attributed to the PPI deficit-ameliorating effects of ATM and that ATM would be useful to treat sensorimotor gating-related disorders by improving the patient's attention span or cognitive function.
authors: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-west Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Hyun
authors: H
authors: Woo
authors: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-west Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Se Jin
authors: SJ
authors: Park
authors: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-west Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Younghwa
authors: Y
authors: Lee
authors: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-west Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Guyoung
authors: G
authors: Kwon
authors: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-west Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Qingtao
authors: Q
authors: Gao
authors: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-west Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Hyung Eun
authors: HE
authors: Lee
authors: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-west Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Young Je
authors: YJ
authors: Ahn
authors: Department of Neuroscience, School of Medicine and Neuroscience Research Center, Institute SMART-IABS, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Chan Young
authors: CY
authors: Shin
authors: Department of Pharmacy, Uimyung Research Institute for Neuroscience, Sahmyook University, Seoul 139-742, Republic of Korea.
authors: Jae Hoon
authors: JH
authors: Cheong
authors: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea; Kyung Hee East-west Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: jhryu63@khu.ac.kr.
authors: Jong Hoon
authors: JH
authors: Ryu
mesh_terms: D000161:Acoustic Stimulation; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D000069445:Atomoxetine Hydrochloride; D001307:Auditory Perception / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D008813:Mice, Inbred ICR; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D065808:Prepulse Inhibition / Q000187:drug effects* / Q000502:physiology; D011437:Propylamines / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D055139:Sensory Gating / Q000187:drug effects* / Q000502:physiology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D011437:Propylamines; D016760:Proto-Oncogene Proteins c-fos; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride; D016291:Dizocilpine Maleate; D001058:Apomorphine
keywords: Atomoxetine; Dopaminergic neurotransmitter system; Methylphenidate; Prepulse inhibition; Sensorimotor gating