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  2. Tetrabenazine, a vesicular monoamine transporter-2 inhibitor, attenuates morphine-induced hyperlocomotion in mice through alteration of dopamine and 5-hydroxytryptamine turnover in the cerebral cortex

Tetrabenazine, a vesicular monoamine transporter-2 inhibitor, attenuates morphine-induced hyperlocomotion in mice through alteration of dopamine and 5-hydroxytryptamine turnover in the cerebral cortex

  • Pharmacol Biochem Behav. 2018 Sep;172:9-16. doi: 10.1016/j.pbb.2018.07.002.
Nobue Kitanaka 1 Junichi Kitanaka 2 F Scott Hall 3 Takashi Kandori 1 Ayaka Murakami 1 Kazuki Muratani 1 Tae Nakano 1 George R Uhl 4 Motohiko Takemura 1
Affiliations

Affiliations

  • 1 Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
  • 2 Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan. Electronic address: kitanaka-hyg@umin.net.
  • 3 Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA.
  • 4 New Mexico VA Healthcare System/BRINM, Albuquerque, NM 87108, USA.
Abstract

A single administration with morphine (30 mg/kg, i.p.) induced long-lasting hyperlocomotion in male ICR mice. Pretreatment of mice with a benzoquinolizine derivative tetrabenazine (TBZ; a reversible vesicular monoamine transporter-2 inhibitor) (1 mg/kg, i.p.) for 30 min significantly attenuated the hyperlocomotion induced by morphine, as compared with vehicle (saline)-pretreated mice. No significant change in locomotion was observed in mice pretreated with TBZ (1 mg/kg) alone. Mice treated with TBZ (1 mg/kg) showed an increase in immobility time in a tail suspension test, as compared with saline-treated mice. Pretreatment with TBZ (1 mg/kg) had no effect on morphine (1-30 mg/kg)-induced antinociception. TBZ at a dose of 1 mg/kg inhibited dopamine turnover (the ratio of 3,4-dihydroxyphenylacetic acid/dopamine) and 5-hydroxytryptamine turnover (the ratio of 5-hydroxyindoleacetic acid/5-hydroxytryptamine) in the cerebral cortex of mice challenged with morphine, as compared with saline-pretreated mice challenged with morphine. No stereotypic behavior was observed in mice treated with morphine (30 mg/kg) in combination with TBZ (1 mg/kg), so the reduction in observed locomotion did not result from induction of stereotypical behavior. Moreover, TBZ (1 and 2 mg/kg) pretreatment had no effect on stereotyped behaviors observed in mice challenged with 10 mg/kg methamphetamine. These data support the potential antagonistic actions of TBZ on some opiate actions, and encourage further exploration of potential effects on morphine reinforcement.

Keywords

5-Hydroxytryptamine turnover; Antinociception; Dopamine turnover; Hyperlocomotion; Morphine; Tetrabenazine.

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