In the central nervous system, cyclooxygenase 2 (COX-2) is a constitutive enzyme,
expressed by neurons from different brain regions, which acts in the maintenance of
neural homeostasis, modulating synaptic plasticity and the generation of new neurons.
Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs of choice that act to inhibit
COX enzymes, with nimesulide (NMS) being a drug of this class. Several studies have
demonstrated the role of these enzymes in neurological and neuropsychiatric disorders
such as Parkinson's Disease, Alzheimer's Disease, epilepsy, depression and
schizophrenia. Thus, the aim of the present work was to investigate the effects of COX-
2 inhibition in healthy infant mice on behavioral and biochemical criteria, using NMS as
a pharmacological blockade tool. For this, male Swiss infant mice, aged between 21 and
34 days, were used. The animals were randomly divided into four groups: (1) Vehicle,
(2) NMS 2.5mg/kg, (3) NMS 5mg/kg and (4) NMS 10mg/kg. Two injections of
NMS/Vehicle were administered intraperitoneally daily. Throughout the experiment, the
body mass of the animals was recorded daily and they were subjected to behavioral tests:
open field test (OFT), elevated plus maze (EPM), light/dark box test (LDBT) and novel
object recognition test (NORT). In addition, brain samples were collected for biochemical
analyses. The results demonstrated the induction of oxidative stress with increased levels
of lipid peroxidation in the cortex and hippocampus, as well as the expression of an
anxiogenic behavior, observed in the EPM, possibly potentiated by fear. In the NORT,
the animals of the NMS 5mg/kg group showed a deficit in the memory of recognizing
new objects, and consequently, in the short-term memory. Thus, our results demonstrated
that the in vivo inhibition of COX-2 in infant animals induces an anxious-like behavior
possibly potentiated by fear, but does not affect the exploration and locomotion of these
animals. Furthermore, COX-2 inhibition induced cortical and hippocampal oxidative
stress. Therefore, the inhibition of COX-2 in infantile and non-inflamed animals may
compromise cognitive functions such as memory and learning, as well as alter the cerebral
oxidative profile.
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