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Postmortem Stability of Monoamines, Their Metabolites, and Receptor Binding in Rat Brain Regibns
Author(s) -
Kontur P. J.,
AlTikriti M.,
Innis R. B.,
Roth R. H.
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.62010282.x
Subject(s) - monoamine neurotransmitter , dopamine , serotonin , raclopride , neurochemical , chemistry , striatum , metabolite , medicine , endocrinology , ketanserin , cortex (anatomy) , cholecystokinin , receptor , 5 ht receptor , biology , biochemistry , neuroscience
The effects of postmortem delay, time of storage, and freezing, thawing, and refreezing tissue samples were studied in postmortem rat brain using conditions that reflect the handling of postmortem human brain before neurochemical analysis. The levels of monoamines and metabolites in the striatum and cingulate and occipital cortex were measured using alumina extraction and HPLC methods. Binding of raclopride to dopamine D 2 , SCH‐ 23390 to dopamine D 1 , ketanserin to serotonin 5‐HT 2 , 8‐ hydroxy‐2‐(di‐ n ‐propylamino)tetralin to serotonin 5‐HT 1A , and cholecystokinin (CCK)‐8 to CCK‐B sites was measured in tissue homogenates from the striatum or frontoparietal cortex. An 18‐h postmortem delay before dissection and storage resulted in region‐specific changes in monoamine and metabolite levels. Binding to striatal D 1 and frontoparietal cortex CCK‐B sites was reduced over the course of a 27‐h postmortem delay. Binding to D 2 and 5‐HT sites was relatively stable. Storage of tissue for up to 8 months also resulted in region‐specific changes in monoamine and metabolite levels. No changes in receptor binding were seen after long‐term storage. Freezing, thawing, and refreezing tissue samples resulted in increased levels of striatal 3, 4‐dihydroxyphenylacetic acid and decreased binding to striatal D 2 sites. These results demonstrate time‐, temperature‐, and storage‐dependent regional differences in.the stability of monoamines and their metabolites and in binding to various receptor sites. These differences in stability and binding should be accounted for to interpret accurately the effects of neurological disorders on neurotransmitter dynamics in postmortem human brain tissue.