Ž . Developmental Brain Research 110 1998 51–59 Research report A comparison of the adenosine-mediated synaptic inhibition in the CA3 area of immature and adult rat hippocampus Severine Descombes a , Massimo Avoli b , Caterina Psarropoulou a, ) a Department of Physiology and Biophysics, Faculty of Medicine, UniÕersity of Sherbrooke, Sherbrooke, QC, Canada J1H 5N4 b Montreal Neurological Institute, Department of Neurology and Neurosurgery and Department of Physiology, McGill UniÕersity, Montreal, QC, Canada H3A 2B4 Accepted 9 June 1998 Abstract Ž . We compared the effects of the adenosine A1 receptor activation on the postsynaptic potentials psps recorded from the CA3 area of Ž . immature postnatal days 10–20 and adult rat hippocampal neurons in vitro. The adenosine A1 receptor agonist 2-phenyl-isopropyl- Ž . adenosine PIA, 1 mM depressed the stimulus-induced psps less in immature and more in adult neurons. In the presence of the GABA A Ž . receptor antagonist bicuculline methiodide BMI, 10 mM , PIA reduced the duration and number of action potentials of the Ž . stimulus-induced paroxysmal depolarizations PDs in immature neurons, while it blocked PDs in adult neurons. Spontaneous Ž . Ž . BMI-induced PDs, were blocked by PIA in less than half 5r12 immature and all 6r6 adult neurons. The adenosine A1 receptor Ž . antagonist 8-cyclopentyl-1,3-dipropylxanthine DPCPX, 1 mM enhanced the stimulus-induced psps in immature and adult neurons alike; Ž . this effect did not lead to stimulus-induced bursting in immature neurons. DPCPX induced spontaneous bursts proconvulsant effect in Ž . only 2r16 immature but in all adult 12r12 neurons. In BMI, DPCPX increased the duration and number of action potentials of the Ž . stimulus-induced PDs in immature and adult neurons alike by about 30% , but it increased the rates of occurrence of spontaneous PDs in significantly more adult neurons. In conclusion, our results suggest that adenosine, acting via A1 receptors, is a more effective endogenous anti-epileptic in adult than in immature hippocampus, a fact which may contribute to the susceptibility of the latter to epileptogenesis. q 1998 Elsevier Science B.V. All rights reserved. Keywords: Adenosine; Development; Hippocampus; Synaptic inhibition; Rat 1. Introduction Adenosine exerts tonic inhibitory effects in the adult w x hippocampus 14,28 by reducing transmitter release from w x excitatory terminals 35–37,39,43 and by modulating in- w x trinsic membrane properties 4,12,15,16 . Adenosine might play a role in the termination of epileptic seizures as its concentration rises substantially following seizures both in wx Ž wx. humans 9 and in animals for review see Ref. 8. Reports on several models of epileptiform activity both in vivo and in vitro have shown that adenosine and its w x analogs inhibit synchronous discharges 3,21,42 , while ) Corresponding author. Ste-Justine Research Center, 3175 Cote Ste- ˆ Catherine, Montreal, QC, Canada H3T 1C5. Fax: q1-514-345-4801; E-mail: caterina@justine.umontreal.ca adenosine antagonists prolong them, promote their spread Ž andror lower their induction threshold proconvulsant ef- . w x fect 8,10 . Hippocampus is a key structure for seizure generation, and its CA3 area acts as the pacemaker of epileptiform Ž w x. activity in immature hippocampus as well 32,33 , possi- bly because of its intrinsic recurrent excitatory connections w x 22,24 . Adenosine A1 receptor antagonists applied in adult w x hippocampal preparations have proconvulsant effects 1–3 , thus showing that endogenous adenosine exerts a strong tonic inhibition in this structure. Immature hippocampus generates sustained synchronous epileptiform discharges in w x response to epileptogenic stimuli 32,38 and one of the several hypotheses that would explain it, would be the immaturity of the tonic inhibition exerted by adenosine, at this period. Therefore, the goal of this work was to com- pare the effects of the adenosine A1 receptor agonist Ž . 2-phenyl-isopropyl-adenosine PIA and the A1 antagonist 0165-3806r98r$19.00 q 1998 Elsevier Science B.V. All rights reserved. Ž . PII: S0165-3806 98 00093-5