RT Journal Article
SR Electronic
T1 Pharmacological Protection of Synaptic Function, Spatial Learning, and Memory from Transient Hypoxia in Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 408
OP 416
DO 10.1124/jpet.300.2.408
VO 300
IS 2
A1 Miao-Kun Sun
A1 Hui Xu
A1 Daniel L. Alkon
YR 2002
UL http://jpet.aspetjournals.org/content/300/2/408.abstract
AB Hypoxia significantly reduced cholinergic θ activity in rat CA1 field and intracellular θ in the CA1 pyramidal cells, recorded in hippocampal slices. The hypoxic responses of the hippocampal CA1 pyramidal cells to a brief hypoxia consisted of a short period of “synaptic arrest”, observed as an elimination of excitatory postsynaptic current under voltage clamp and recovered immediately as oxygenation was reinitiated. The hypoxic synaptic arrest was not associated with reduced postsynaptic responses of the pyramidal cells to externally applied l-glutamate, suggesting that the synaptic arrest might result from a presynaptic mechanism. The hypoxic synaptic arrest was abolished in the presence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific adenosine A1 receptor antagonist. Blocking adenosine A1receptors also eliminated effects of hypoxia on the hippocampal CA1 field θ activity and intracellular θ of the CA1 pyramidal cells. In behaving rats, brief hypoxia impaired their water maze performance in both the escape latency and probe tests. The impairment was prevented by intralateral cerebroventricular injections of DPCPX. These results suggest that hypoxia releases adenosine and produces an inhibition of synaptic transmission and intracellular signal cascade(s) involved in generation/maintenance of hippocampal CA1 θ activity. This protection of synaptic efficacy and spatial learning through adenosine A1 receptor antagonism may represent an effective therapeutic strategy to eliminate functional interruption due to transient hypoxic episodes and/or chronic hypoxia secondary to compromise of respiratory function. The American Society for Pharmacology and Experimental Therapeutics