Kainic acid lesions enhance locomotor responses to novelty, saline, amphetamine, and MK-801.

Intracerebroventricular (i.c.v.) administration of kainic acid (KA) to rats produces neuronal loss in the hippocampus and other areas of the limbic system. The present study demonstrates that i.c.v. KA enhances the locomotor response to novelty and saline injection, as well as to amphetamine and MK-801. Sixteen to 18 days after i.c.v. administration of KA or vehicle, lesioned and control rats were placed in a novel cage, and locomotor activity and grooming were recorded for 30 min prior to and 60 min following a subcutaneous injection of saline, D-amphetamine, or MK-801. In response to the novel cage and after each injection, KA rats exhibited increased locomotor activity relative to controls. Grooming behavior was found to be elevated in the KA rats when compared to controls, but only in response to the novel cage and saline injection. The possibility that damage to the limbic system disrupts dopaminergic regulation of locomotor behavior is discussed, as well as implications for neuropathology in schizophrenia.