Modafinil in comparison with DSP4 in altering tail pinch-induced sensorimotor gating effects in rats

Background: Pre-pulse inhibition of acoustic startle is thought to reflect sensorimotor gating effects, which has proven to be a useful model system for studying effects of psychostimulant drugs in psychopharmacology. A variety of drugs or stressors have been reported to modulate the sensorimotor gating reactivity by altering brain catecholamine neuron activities. Modafinil is a drug increasingly used as a medication for elevating arousal and vigilance, yet its underlying mechanisms are still not fully understood. The purpose of the present study was to determine whether or not brain catecholamine neurons are involved in modafinil's effects on sensorimotor gating reactivity. Methods: Rats were divided into three groups, i.e. the pretreatment with modafinil (64 mg/kg, i.p.) group, the selective lesion of the brain dorsal noradrenergic bundle with neurotoxin DSP4 (50 mg/kg, i.p.) group, and the saline control group. A further experiment was performed to verify whether or not the effect of modafinil is counteracted by an effective dose of haloperidol (0.1 mg/kg, s.c). All rats were measured by PPI of the acoustic startle, including a session in which subjects were exposed to tail-pinch (TP) and the sessions before or after TP. Results: The results showed that rats of both the modafinil and DSP4 pretreated groups exhibited the same pattern of effects in enhancing TP-induced PPI disruption. However, a difference was also observed. The induced reduction in PPI was accompanied with a significant elevation of the startle magnitude in the DSP4 group but not in modafinil pretreated group. In addition, further experiment results indicated that a dopamine D2 antagonist, haloperidol, significantly normalized the modafinil-induced PPI disruptive effects. Conclusion: These findings suggest that modafinil might precipitate sensorimotor gating deficits in rats confronted by TP stress, similar to the DSP4 pretreated group rats. In respect to these two catecholamine substrates, dopamine and norepinephrine, the PPI effects of modafinil on dopaminergic neurons are substantiated the present study. On the other hand, more experiments are needed to confirm the related mechanisms of noradrenergic neurons in the effects of modafinil.