Therapeutic potential of nicotine for methamphetamine-induced impairment of sensorimotor gating: involvement of pallidotegmental neurons.

Introduction: 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.

Objectives: 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.