Abstract：
:Autoradiographic techniques were used to test if positive modulators of AMPA-type glutamate receptors have regionally differentiated effects on ligand binding. Cyclothiazide, a drug with ten fold greater effects on 'flip' than 'flop' splice variants of the receptors, had unequal effects across the subdivisions of hippocampus; i.e., it reduced [3H]AMPA binding in field CA3 with an EC50 of 24 microM and in field CA1 and dentate gyrus with EC50s between 60 and 100 microM. The EC50 for the drug's influence on binding was also significantly lower in the superficial than in the deeper layers of the neocortex, though these differences were not as pronounced as those in the hippocampus. The ampakine CX614, a compound with a modest preference for flop variants, had a slightly lower EC50 for its effects on [3H]AMPA binding in CA1 than in CA3. This result was confirmed with [3H]fluorowillardiine binding. The effects of the ampakine in neocortex tended to be greater in the deeper than superficial layers but this did not reach statistical significance. These results indicate that differential effects of modulators on AMPA receptor subunits are reflected in their relative potency across brain subdivisions. This raises the possibility that subclasses of positive modulators will exhibit a measurable degree of selectivity in their physiological and behavioral influences.
journal_name
Brain Resjournal_title
Brain researchauthors
Kessler M,Mutneja MS,Rogers G,Lynch Gdoi
10.1016/s0006-8993(97)01315-2subject
Has Abstractpub_date
1998-02-02 00:00:00pages
121-6issue
1eissn
0006-8993issn
1872-6240pii
S0006-8993(97)01315-2journal_volume
783pub_type
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