Chronic moderate hyperammonemia impairs active and passive avoidance behavior and conditional discrimination learning in rats.

The cerebral dysfunction associated with hepatic encephalopathy is generally considered to have hyperammonemia as one of its main causes. Hyperammonemia impairs the neuronal glutamate-nitric oxide-cyclic GMP pathway and the induction of NMDA receptor-dependent long-term potentiation in the hippocampus. We studied the performance of pre/neonatally and postnatally exposed rats to hyperammonemia on active avoidance, passive avoidance, and conditional discrimination tasks. Pre/neonatal hyperammonemia slowed learning of active avoidance behaviors and impaired memory for the passive avoidance task while postnatal hyperammonemia impaired learning on the conditional discrimination task. Hyperammonemia thus may produce cognitive disturbances that relate to the effects of ammonia on the neuronal glutamate-nitric oxide-cyclic GMP pathway.