POTENTIATION OF LEARNING IMPAIRMENT OF ACETAZOLAMIDE BY AMILORIDE IN RATS

Objectives: Acetazolamide (AZ), an adjuvant antiepileptic drug for intractable and catamenial epilepsy in human, impaired spatial learning in rats. In addition, AZ causes metabolic acidosis. We here investigated its interaction with amiloride (AM), a nonselective acidsensitive ion channel blocker, on learning behavior.

Methods: Male adult Wistar rats, weighing 300–400g, were randomly assigned into three groups: control group (normal saline), AZ group and AZ+AM group (10mg/kg for AM). Shuttle-avoidance test was started by the conditioned stimulus (CS, light+ 85 dB voice) lasting for 3s. The unconditioned stimulus (UCS) was a 2s 0.8 mA foot shock delivered to the grid floor. In trials, the UCS was followed by the CS, and the inter-stimulus interval was 25s. The avoid response was recorded as if the rats escaped the shock by running from one compartment to the other one within 3s after the CS. Morris water maze was as another learning model. Startle response to electric shock was applied to rule out the interference on sensation by drugs.

Results: The mean avoidance rates on Day-4 of the shuttle avoidance test were as follows: 31.1% in control group, 3.8% in AZ (60mg/kg) group and 3.1% in AZ+AM group. The potentiation of learning impairment by AM was also clearly observed in response to lower dose of AZ (10mg/kg). The startle responses to electric shock and sound were not affected by AZ and AZ+AM. Amiloride also enhanced the impairment of learning behavior by AZ during Morris water maze. Conclusion: Amiloride may interact with AZ to affect the metabolism of CO2 and acidity of intracellular pH and thus the synaptic plasticity of neuronal cells.