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.
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 GABA(B) 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 GABA(B) 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. GABA(B) receptor may constitute a putative target in treating neuropsychiatric disorders with sensorimotor gating deficits, such as schizophrenia and METH psychosis.
Arai
Sawako
S
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan.
Takuma
Kazuhiro
K
Mizoguchi
Hiroyuki
H
Ibi
Daisuke
D
Nagai
Taku
T
Takahashi
Kenji
K
Kamei
Hiroyuki
H
Nabeshima
Toshitaka
T
Yamada
Kiyofumi
K
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D011149:Pons / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism; D012154:Reticular Formation / Q000187:drug effects* / Q000378:metabolism; D055139:Sensory Gating / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D058786:GABA-B Receptor Agonists; D016760:Proto-Oncogene Proteins c-fos; D018080:Receptors, GABA-B; D008694:Methamphetamine; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D001418:Baclofen