Intracortical Injection of Okadaic Acid Increases Locomotor Activity and Decreases Anxiety-like Behaviour in Adult Male Rats: Potential Involvement of NMDA Receptor.

Background: Neuronal transmission through the N-methyl-d-aspartate receptor (NMDAR) is a key event in synaptic plasticity and excitotoxicity. The channel properties and biochemical signalling activities of the receptor are regulated by phosphatases such as protein phosphatase 1. While the immediate consequences of NMDAR activation have been reported previously, the long-term behavioural changes remain unclear.

Purpose: We attempted to investigate the long-term behavioural effects of N-methyl-d-aspartic acid (NMDA) injection and the role of phosphatases during NMDAR signalling.

Methods: NMDAR was activated by stereotaxic injection of NMDA into the prefrontal cortex of adult rats. To elucidate the role of phosphatases in mediating NMDAR signalling and associated animal behaviour, okadaic acid (OA), a phosphatase inhibitor, was administered before NMDA injection. The animals were tested for their general locomotion and cognitive function using behavioural assays.

Results: A single injection of NMDA impaired cognition in the long term. Interestingly, intracortical OA injection resulted in increased locomotor activity and decreased anxiety-like behaviour in animals without major cognitive effects.

Conclusion: We demonstrate that the inhibition of phosphatases during NMDAR signalling can affect locomotion and anxiety-like behaviour in adult male rats. Our study underscores the potential of modulating phosphatases as a pharmacological target for anxiety disorders.