Presynaptic inhibitory receptors mediate the depression of synaptic transmission upon hypoxia in rat hippocampal slices

Hypoxia markedly depresses synaptic transmission in hippocampal slices of t he rat. This depression is attributed to presynaptic inhibition of glutamat e release and is largely mediated by adenosine released during hypoxia acti ng through presynaptic adenosine A(1) receptors. Paired pulse facilitation studies allowed us to confirm the presynaptic nature of the depression of s ynaptic transmission during hypoxia. We tested the hypothesis that activati on of heterosynaptic inhibitory receptors localized in glutamategic presyna ptic terminals in the hippocampus, namely gamma-aminobutyric acid subtype B (GABA(B)) receptors, alpha(2)-adrenergic receptors, and muscarinic recepto rs might contribute to the hypoxia-induced depression of synaptic transmiss ion. Field excitatory postsynaptic potentials were recorded in the CA1 area of hippocampal slices from young adult (5-6 weeks) Wistar rats. Neither th e selective antagonist for alpha(2)-adrenergic receptors, rauwolscine (10 m u M), nor the antagonist for the GABA(B) receptors, CGP 55845 (10 mu M), mo dified the response to hypoxia. The selective adenosine A(1) receptor antag onist, DPCPX (50 nM), reduced the hypoxia-induced depression of synaptic tr ansmission to 59.2+/-9.6%, and the muscarinic receptor antagonist, atropine (10 mu M), in the presence of DPCPX (50 nM), further attenuated the depres sion of synaptic transmission to 49.4+/-8.0%. In the same experimental cond itions, in the presence of DPCPX (50 nM), the muscarinic M-2 receptor antag onist AF-DX 116 (10 mu M), but not the M-1 receptor antagonist pirenzepine (1 mu M), also attenuated the hypoxia-induced depression to 41.6+/-6.6%. Ac tivation of muscarinic M-2 receptors contributes to the depression of synap tic transmission upon hypoxia. This effect should assume particular relevan ce during prolonged periods of hypoxia when other mechanisms may become les s efficient. (C) 2000 Elsevier Science B.V. All rights reserved.