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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+Show Affiliations

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.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.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.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.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.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.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.Department of Neuroscience, School of Medicine and Neuroscience Research Center, Institute SMART-IABS, Konkuk University, Seoul 143-701, Republic of Korea.Department of Pharmacy, Uimyung Research Institute for Neuroscience, Sahmyook University, Seoul 139-742, Republic of Korea.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24953433

Citation

Woo, Hyun, et al. "The Effects of Atomoxetine and Methylphenidate On the Prepulse Inhibition of the Acoustic Startle Response in Mice." Progress in Neuro-psychopharmacology & Biological Psychiatry, vol. 54, 2014, pp. 206-15.
Woo H, Park SJ, Lee Y, et al. The effects of atomoxetine and methylphenidate on the prepulse inhibition of the acoustic startle response in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2014;54:206-15.
Woo, H., Park, S. J., Lee, Y., Kwon, G., Gao, Q., Lee, H. E., Ahn, Y. J., Shin, C. Y., Cheong, J. H., & Ryu, J. H. (2014). The effects of atomoxetine and methylphenidate on the prepulse inhibition of the acoustic startle response in mice. Progress in Neuro-psychopharmacology & Biological Psychiatry, 54, 206-15. https://doi.org/10.1016/j.pnpbp.2014.06.003
Woo H, et al. The Effects of Atomoxetine and Methylphenidate On the Prepulse Inhibition of the Acoustic Startle Response in Mice. Prog Neuropsychopharmacol Biol Psychiatry. 2014 Oct 3;54:206-15. PubMed PMID: 24953433.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of atomoxetine and methylphenidate on the prepulse inhibition of the acoustic startle response in mice. AU - Woo,Hyun, AU - Park,Se Jin, AU - Lee,Younghwa, AU - Kwon,Guyoung, AU - Gao,Qingtao, AU - Lee,Hyung Eun, AU - Ahn,Young Je, AU - Shin,Chan Young, AU - Cheong,Jae Hoon, AU - Ryu,Jong Hoon, Y1 - 2014/06/20/ PY - 2014/03/06/received PY - 2014/05/30/revised PY - 2014/06/11/accepted PY - 2014/6/24/entrez PY - 2014/6/24/pubmed PY - 2015/5/13/medline KW - Atomoxetine KW - Dopaminergic neurotransmitter system KW - Methylphenidate KW - Prepulse inhibition KW - Sensorimotor gating SP - 206 EP - 15 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog Neuropsychopharmacol Biol Psychiatry VL - 54 N2 - 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. SN - 1878-4216 UR - https://www.unboundmedicine.com/medline/citation/24953433/The_effects_of_atomoxetine_and_methylphenidate_on_the_prepulse_inhibition_of_the_acoustic_startle_response_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-5846(14)00122-5 DB - PRIME DP - Unbound Medicine ER -