The neuromatrix and the epileptic brain: behavioral and learning preservation in limbic epileptic rats treated with ketamine but not acepromazine.
Conceiving the organization of the brain as a "neuromatrix" could provide significant insights into how different injuries to the nervous system could result in very distinct changes in behavior. The use of different pharmacological treatments to combat the deleterious consequences of such injuries is common practice. However, such treatments may have the capacity to alter the configurations of various neuronal circuits that contribute to the "neuromatrix" by selectively preventing damage to some pathways while facilitating the spread of destruction along others. The choice of pharmacological treatment may have profound consequences on the recovery of normal functioning following injury. We examined the behavior of rats treated with one of two potentially neuroprotective agents, the N-methyl-D-aspartate antagonist ketamine and the atypical neuroleptic acepromazine, on seizures induced by lithium-pilocarpine. Rats treated with ketamine following seizure onset were virtually indistinguishable from nonepileptic controls on a variety of behavioral tasks that included tests on learning, memory, and anxiety. In contrast, acepromazine-treated rats showed marked deficits on all learning and behavioral measures tested. These results suggest that administration of ketamine relatively soon after the emergence of epilepsy can prevent many of the cognitive deficits that are commonly found in rats subjected to lithium-pilocarpine-induced seizures. Further clinical testing investigating ketamine as a potential adjunct treatment for epilepsy may be well warranted.
Fournier
N M
NM
Behavioral Neuroscience Laboratory, Laurentian University, Sudbury, Ontario, Canada. fournien@dal.ca
Persinger
M A
MA
D000075:Acepromazine / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D016009:Chi-Square Distribution; D003213:Conditioning, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D004827:Epilepsy / Q000150:complications / Q000378:metabolism; D004924:Escape Reaction / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology* / Q000627:therapeutic use; D018021:Lithium Chloride; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D013997:Time Factors
D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D000075:Acepromazine; D007649:Ketamine; D018021:Lithium Chloride