Involvement of pallidotegmental neurons in methamphetamine- and MK-801-induced impairment of prepulse inhibition of the acoustic startle reflex in mice: Reversal by GABAB receptor agonist baclofen

Sawako Arai, Kazuhiro Takuma, Hiroyuki Mizoguchi, Daisuke Ibi, Taku Nagai, Kenji Takahashi, Hiroyuki Kamei, Toshitaka Nabeshima, Kiyofumi Yamada

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

We have previously demonstrated that pallidotegmental GABAergic neurons play a crucial role in prepulse inhibition (PPI) of the startle reflex in mice through the activation of GABAB receptors in pedunculopontine tegmental neurons. In this study, we investigated whether PPI disruption induced by methamphetamine (METH) or MK-801 is associated with the dysfunction of pallidotegmental neurons. Furthermore, we examined the effects of baclofen, a GABAB receptor agonist, on METH- and MK-801-induced PPI impairment. Acute treatment with METH (3 mg/kg, subcutaneouly (s.c.)) and MK-801 (>0.3 mg/kg, s.c.) significantly disrupted PPI, accompanied by the suppression of c-Fos expression in lateral globus pallidus induced by PPI. Furthermore, acute treatment with METH and MK-801 stimulated c-Fos expression in the caudal pontine reticular nucleus (PnC) in mice subjected to the PPT test, although PPI alone had no effect on c-Fos expression. Repeated treatment with 1 mg/kg METH for 7 days, which did not affect PPI acutely, showed similar effects on PPI and c-Fos expression to acute treatment with METH (3 mg/kg). Baclofen dose-dependently ameliorated PPI impairment induced by acute treatment with METH (3 mg/kg) and MK-801 (1 mg/kg), and decreased METH- and MK-801-stimulated c-Fos expression in PnC to the basal level. These results suggest that dysfunction of pallidotegmental neurons is involved in PPI disruption caused by METH and MK-801 in mice. GABAB receptor may constitute a putative target in treating neuropsychiatric disorders with sensorimotor gating deficits, such as schizophrenia and METH psychosis.

Original languageEnglish
Pages (from-to)3164-3175
Number of pages12
JournalNeuropsychopharmacology
Volume33
Issue number13
DOIs
Publication statusPublished - 01-12-2008
Externally publishedYes

Fingerprint

Startle Reflex
GABA-B Receptors
Dizocilpine Maleate
Methamphetamine
Neurons
Baclofen
Prepulse Inhibition
Sensory Gating
Therapeutics
GABAergic Neurons
Globus Pallidus
Basal Ganglia
Psychotic Disorders
Schizophrenia

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Arai, Sawako ; Takuma, Kazuhiro ; Mizoguchi, Hiroyuki ; Ibi, Daisuke ; Nagai, Taku ; Takahashi, Kenji ; Kamei, Hiroyuki ; Nabeshima, Toshitaka ; Yamada, Kiyofumi. / Involvement of pallidotegmental neurons in methamphetamine- and MK-801-induced impairment of prepulse inhibition of the acoustic startle reflex in mice : Reversal by GABAB receptor agonist baclofen. In: Neuropsychopharmacology. 2008 ; Vol. 33, No. 13. pp. 3164-3175.
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abstract = "We have previously demonstrated that pallidotegmental GABAergic neurons play a crucial role in prepulse inhibition (PPI) of the startle reflex in mice through the activation of GABAB receptors in pedunculopontine tegmental neurons. In this study, we investigated whether PPI disruption induced by methamphetamine (METH) or MK-801 is associated with the dysfunction of pallidotegmental neurons. Furthermore, we examined the effects of baclofen, a GABAB receptor agonist, on METH- and MK-801-induced PPI impairment. Acute treatment with METH (3 mg/kg, subcutaneouly (s.c.)) and MK-801 (>0.3 mg/kg, s.c.) significantly disrupted PPI, accompanied by the suppression of c-Fos expression in lateral globus pallidus induced by PPI. Furthermore, acute treatment with METH and MK-801 stimulated c-Fos expression in the caudal pontine reticular nucleus (PnC) in mice subjected to the PPT test, although PPI alone had no effect on c-Fos expression. Repeated treatment with 1 mg/kg METH for 7 days, which did not affect PPI acutely, showed similar effects on PPI and c-Fos expression to acute treatment with METH (3 mg/kg). Baclofen dose-dependently ameliorated PPI impairment induced by acute treatment with METH (3 mg/kg) and MK-801 (1 mg/kg), and decreased METH- and MK-801-stimulated c-Fos expression in PnC to the basal level. These results suggest that dysfunction of pallidotegmental neurons is involved in PPI disruption caused by METH and MK-801 in mice. GABAB receptor may constitute a putative target in treating neuropsychiatric disorders with sensorimotor gating deficits, such as schizophrenia and METH psychosis.",
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Involvement of pallidotegmental neurons in methamphetamine- and MK-801-induced impairment of prepulse inhibition of the acoustic startle reflex in mice : Reversal by GABAB receptor agonist baclofen. / Arai, Sawako; Takuma, Kazuhiro; Mizoguchi, Hiroyuki; Ibi, Daisuke; Nagai, Taku; Takahashi, Kenji; Kamei, Hiroyuki; Nabeshima, Toshitaka; Yamada, Kiyofumi.

In: Neuropsychopharmacology, Vol. 33, No. 13, 01.12.2008, p. 3164-3175.

Research output: Contribution to journalArticle

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T2 - Reversal by GABAB receptor agonist baclofen

AU - Arai, Sawako

AU - Takuma, Kazuhiro

AU - Mizoguchi, Hiroyuki

AU - Ibi, Daisuke

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AU - Takahashi, Kenji

AU - Kamei, Hiroyuki

AU - Nabeshima, Toshitaka

AU - Yamada, Kiyofumi

PY - 2008/12/1

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