7-Nitroindazole blocks the prepulse inhibition disruption and c-Fos increase induced by methylphenidate

The dopamine and nitric oxide (NO) interaction on sensorimotor gating modulation measured through the prepulse inhibition (PPI), has been described recently. The PPI impairment has been reported in several neuropsychiatric conditions, particularly in schizophrenia. We previously demonstrated that NO inhibitors, similarly to the antipsychotic drugs, attenuate the disruptive effect of amphetamine or its analogue methylphenidate in the PPI response.

Our aim was to determine if the known expression of the neuronal activity marker c-Fos induced by methylphenidate may be modified by NO inhibition. Mice were treated with the PPI-disruptive dose of methylphenidate (30 mg/kg) preceded by pretreatment with saline, or the dose of preferential neuronal NO inhibitor 7-Nitroindazole (7NI; 10 mg/kg) which promotes PPI recovery.

Acute treatment with methylphenidate at dose that caused PPI disruption induced a robust increase in the number of c-Fos-positive cells in the cingulate and motor cortex, dorsal, dorsolateral, and ventrolateral striatum, nucleus accumbens core and shell, and basolateral amygdala. In the animals which presented PPI recovery through 7NI pretreatment, the c-Fos increase induced by methylphenidate was significantly reduced in the cingulate cortex (rostral level), striatum, mainly dorsal and ventrolateral, nucleus accumbens (core and shell), and in the basolateral amygdala.

Our results suggest that 7NI effects appear to be related to its ability to prevent the activation of specific brain areas, including nucleus accumbens and amygdala, counteracting the stimulant effects of methylphenidate in these regions.