Spatial memory impairments observed in
Alzheimer's disease and
schizophrenia have been attributed to many factors, including
glutamate hypofunction and reduced hippocampal volume.
Clonidine, a non-specific alpha(2)
adrenergic receptor agonist, improves spatial memory in animals treated with the
N-methyl-D-aspartate (
NMDA) receptor antagonist,
phencyclidine; however, its effects on
memory deficits produced by other
NMDA antagonists or hippocampal damage have not been fully characterized. The purpose of this study was to determine if
clonidine could alleviate
memory deficits produced by the
NMDA antagonist,
MK-801, or by excitotoxic hippocampal damage. In the first phase of the study, male rats were pretreated with
clonidine (0.01 or 0.05 mg/kg) or saline, and treated with
MK-801 (0.1 mg/kg) or saline prior to discrete-trial delayed alternation or radial-arm maze testing.
MK-801 impaired delayed alternation performance and increased the number of arm revisits in the radial-arm maze.
Clonidine pretreatment significantly alleviated these drug-induced deficits. In the second phase of the study, excitotoxic damage was produced in the dorsal hippocampus with
NMDA. Hippocampal damage produced a significant impairment in the delayed alternation task, yet pretreatment with
clonidine did not alleviate this damage-induced deficit. Taken together, the data indicate that
clonidine alleviates memory impairments produced by
glutamate hypofunction, but not by hippocampal damage. This caveat may be important in designing treatments for
memory disorders not linked to a single pathophysiological mechanism.