Acetazolamide impairs fear memory consolidation in rodents

Acetazolamide (AZ) is an carbonic anhydrase inhibitor, which has been used in the treatment of seizures, mountain sickness and glaucoma. Memory impairment by AZ has been reported in patient interviews; however, the related mechanism is unclear. We applied two fear conditioning paradigms, shuttle avoidance and passive avoidance, in both rats and mice to investigate this clinical anecdote. Adult Wistar rats receiving AZ 1 h before the shuttle avoidance test showed decreased avoidance rates, especially at high dosage. Adult ICR mice receiving AZ both before and after acquisition trials showed the decreased step-through latencies during the passive avoidance test. This impairment of fear memory was corroborated with decreased LTP by AZ in the amygdala. AZ only inhibited fear conditioning-induced ERK phosphorylation and had no effect on Akt phosphorylation. In conclusion, our study confirmed the adverse cognitive effect of AZ in animal and electrophysiological studies. In clinical practice, clinicians should be aware of this side effect in patients taking AZ. In addition, this inhibition of fear memory by AZ could potentially be applied to patients with posttraumatic stress disorder.