The involvement of adenosine neuromodulation in pentobarbital-induced field excitatory postsynaptic potentials depression in rat hippocampal slices

We investigated the contribution of adenosine neuromodulation to mechanisms of pentobarbital-induced depression of excitatory synaptic transmission in vitro. Transverse hippocampal slices were prepared from brains removed fro m isoflurane-anesthetized male Wistar rats. Field excitatory postsynaptic p otentials (fEPSPs), elicited by orthodromic electrical stimulation of Schaf fer collateral at 0.05 Hz, were recorded from the CA1 region in oxygenated artificial cerebrospinal fluid. Amplitude of fEPSP was analyzed for assessi ng drug effects. Pentobarbital (100 muM) transiently depressed fEPSPs (P < 0.01); i.e., fEPSP was initially depressed to approximately 60% of control and then recovered to approximately 80% of control. The fEPSP depression wa s partially suppressed by pretreatment with 50 <mu>M aminophylline, a nonse lective adenosine receptor antagonist, and 0.2 muM 3,7-Dimethyl-1-plopagylx anthine, an adenosine A, receptor antagonist (P < 0.01 each). However, the fEPSP depression was not affected by pretreatment with 10 <mu>M 8-cyclopent yl-1,3-dipropylxanthine, an A(1) receptor antagonist, or 10 muM bicuculline , a gamma -aminobutyric acid (GABA) A receptor antagonist. The results indi cate that adenosine neuromodulation through A(1) receptors and other undefi ned mechanisms, which are independent from GABAergic mechanisms, are involv ed in pentobarbital-induced depression of excitatory synaptic transmission.