ArticlePsychopharmacology2025
The nitric oxide synthase inhibitor 7-nitroindazole attenuates social withdrawal and memory impairments induced by Blockade of the NMDA receptor in the rat.
Article in Psychopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
rationaleThat exaggerated production of the gaseous molecule nitric oxide (NO) is associated with the pathogenesis of schizophrenia is well-documented. Therefore, compounds that can adjust nitrergic activity such as NO synthase (NOS) inhibitors might be useful for the treatment of schizophrenia.
objectivesThe purpose of the current study was to investigate in the rat the ability of the neuronal NOS (nNOS) inhibitor 7-nitroindazole (7-NI) in counteracting schizophrenia-like-deficits caused by blockade of the N-methyl-D-aspartate (NMDA) receptor.
methods7NI's capacity to attenuate social withdrawal, disruption of emotional and recognition memory induced by NMDA receptor antagonists, namely ketamine and MK-801, were evaluated using the social interaction, the step-through passive avoidance, the object recognition and the object location tests. The efficacy of the joint administration of sub-threshold doses of 7-NI with those of the atypical neuroleptics clozapine and risperidone in attenuating recognition memory deficits induced by ketamine was also tested.
results7-NI (1 and 3 mg/kg) alleviated social withdrawal caused by ketamine (8 mg/kg), abolished emotional memory impairments caused by MK-801 (0.1 mg/kg) and counteracted ketamine (3 mg/kg)-induced recognition memory deficits. Finally, co-administration of inactive doses of 7-NI (0.1 mg/kg) with those of clozapine (0.1 mg/kg) or risperidone (0.03 mg/kg) reduced the detrimental effects of ketamine (3 mg/kg) on recognition memory.
conclusionsThe present results indicate that 7-NI is sensitive to glutamate blockade since it decreased behavioural impairments resembling the negative symptoms and cognitive deficits of schizophrenia. Moreover, these findings corroborate the potential of 7-NI as an adjunctive molecule for the medication of schizophrenia.
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