Therapeutic potential of nicotine for methamphetamine-induced impairment of sensorimotor gating: involvement of pallidotegmental neurons.
BACKGROUND
We have previously found that a disruption to prepulse inhibiton (PPI) induced by methamphetamine (METH) is associated with impaired functioning of pallidotegmental neurons, which play a crucial role in PPI of the startle reflex, through the activation of gamma-aminobutyric acid type B receptors in pedunculopontine tegmental neurons in mice.


OBJECTIVE
Here, we examined the effect of nicotine on METH-induced impairment of PPI of the startle reflex focusing on dysfunctional pallidotegmental neurons and the neural system.


RESULTS
Nicotine (0.15-0.5 mg/kg) ameliorated the deficit in PPI induced by acute METH, and the ameliorating effect of nicotine was antagonized by nicotinic receptor antagonists such as methyllycaconitine and dihydro-beta-erythroidine. The acute METH-induced disruption of PPI was accompanied by suppression of c-Fos expression in the lateral globus pallidus (LGP) as well as its induction in the caudal pontine reticular nucleus (PnC) in mice subjected to the PPI test. Nicotine-induced amelioration of PPI deficits in METH-treated mice was accompanied by a reversal of the changes in c-Fos expression in both the LGP and PnC to the basal level.


CONCLUSIONS
Nicotine is effective in ameliorating the impairment of PPI caused by METH, which may be associated with normalization of the pallidotegmental neurons.
Mizoguchi
Hiroyuki
H
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, 920-1192, Japan.
Arai
Sawako
S
Koike
Hiroyuki
H
Ibi
Daisuke
D
Kamei
Hiroyuki
H
Nabeshima
Toshitaka
T
Kim
Hyoung-Chun
HC
Takuma
Kazuhiro
K
Yamada
Kiyofumi
K
D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D045042:Pedunculopontine Tegmental Nucleus / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects; D055139:Sensory Gating / Q000187:drug effects
D000697:Central Nervous System Stimulants; D018722:Nicotinic Agonists; D016760:Proto-Oncogene Proteins c-fos; D018080:Receptors, GABA-B; D008694:Methamphetamine; D009538:Nicotine