The deleterious effects of aging and kainic acid may be selective for similar striatal neuronal populations.
The present experiments were performed to determine whether the age-related loss of striatal D2 receptors could be localized to a kainic acid-sensitive neuronal population. This neurotoxin selectively destroys intrinsic neurons. Thus, if kainic acid reduced striatal D2 receptor concentrations such that age differences in this parameter were no longer observed, it would be a good indication that the D2 receptors lost through aging are also sensitive to kainic acid. Mature (6 months) and senescent (24 months) rats were stereotaxically, unilaterally injected with 3 micrograms/0.5 microliter kainic acid into the right striatum. Seven days later striatal D2 receptors were assessed with [3H]-spiperone in one group of mature and senescent rats. A second group of mature and senescent unilaterally lesioned rats was anesthetized and perfused. Brains were dissected and processed for striatal cell counts using cresyl violet staining, tyrosine hydroxylase and met-enkephalin using immunocytochemistry, and acetylcholinesterase using histochemistry. Age-related differences in D2-receptor concentrations were observed in intact, but not lesioned, striata. Kainic acid was less effective in reducing D2-receptor concentrations in senescent animals, suggesting that some proportion of the receptors was already lost prior to lesioning. Kainic acid also reduced total neuronal numbers, as well as Met-Enk and AChE positive staining, to approximately the same extent in mature and senescent rats. No age differences were seen in any of the other parameters following kainic acid administration.
Molecular Physiology and Genetics Section, Gerontology Research Center/NIA, Francis Scott Key Medical Center, Baltimore, Maryland 21224.
J A
JA
Joseph
M
M
Gupta
Z
Z
Han
G S
GS
Roth
D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004744:Enkephalin, Methionine / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D017448:Receptors, Dopamine D2; D004744:Enkephalin, Methionine; D014446:Tyrosine 3-Monooxygenase; D000110:Acetylcholinesterase; D007608:Kainic Acid