Ž . European Journal of Pharmacology 331 1997 9–14 8-Cyclopentyltheophylline, an adenosine A receptor antagonist, inhibits 1 the reversal of long-term potentiation in hippocampal CA1 neurons Satoshi Fujii a, ) , Yuko Sekino b , Yoichiro Kuroda c , Hiroshi Sasaki a , Ken-Ichi Ito a , Hiroshi Kato a a Department of Physiology, Yamagata UniÕersity School of Medicine, Yamagata 990-23, Japan b Department of Neurobiology and BehaÕior, Gunma UniÕersity School of Medicine, Maebashi, Gunma 371, Japan c Department of Molecular and Cellular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, 2-6, Musashidai, Fuchu-shi, Tokyo 183, Japan Received 28 January 1997; accepted 21 May 1997 Abstract Ž . The effects of an adenosine A receptor antagonist, 8-cyclopentyltheophylline 8-CPT, 1 mM , on the reduction of long-term 1 Ž . potentiation were studied in CA1 neurons of guinea pig hippocampal slices. Reduction of long-term potentiation depotentiation was Ž . achieved by delivering a train of low-frequency afferent stimuli low-frequency stimulation, 1000 pulses, 1 Hz 20 min after the tetanus Ž . 100 Hz, 100 pulses . In control experiments, low-frequency stimulation reduced the potentiated component of the slope of the field EPSP Ž . and the amplitude of the population spike by 68.5 "14.4% and 80.1 "8.8%, respectively n s6 ; these values were significantly Ž . Ž reduced to 13.4 "9.7% and 9.0 "10.9% n s7 when the low-frequency stimulation was applied during the perfusion with 8-CPT 1 . mM . These results indicate that activation of adenosine A receptors enhances the depotentiation of long-term potentiation. q 1997 1 Elsevier Science B.V. Ž . Keywords: Long-term potentiation; Depotentiation; Adenosine A receptor antagonist; 8-CPT 8-cyclopentyltheophylline ; Synaptic plasticity, modulation 1 of; Hippocampal CA1 neuron 1. Introduction Long-term potentiation is a state of persistent synaptic enhancement induced by a brief period of a high-frequency Ž . Ž electrical stimulation tetanus of afferents Bliss and . Lømo, 1973; Bliss and Gardner-Medwin, 1973 . In addi- tion to long-term potentiation, another type of synaptic plasticity, ‘depotentiation’, has been reported, in which Ž low-frequent afferent stimulation low-frequency stimula- . tion effectively reverses a pre-established long-term Ž potentiation, both in vivo Barrioneuvo et al., 1980; Staubli ¨ . Ž and Lynch, 1990 and in vitro Fujii et al., 1991; Bashir . and Collingridge, 1994; Staubli and Lynch, 1996 . These ¨ activity-dependent synaptic plasticities have been sug- gested to be responsible for important processes involved Ž in the cellular basis of memory and learning Collingridge, 1987; Collingridge and Bliss, 1987; Bliss and Collingridge, . 1993 . ) Ž . Corresponding author. Fax: 81-236 285-221; e-mail: sfujii@med.id.yamagata-u.ac.jp During delivery of input stimulation to hippocampal CA1 neurons, a significant amount of ATP and adenosine derivatives is released from presynaptic terminals into the Ž synaptic cleft in a frequency-dependent manner White, . 1978; Schubert et al., 1979; Wieraszko et al., 1989 . In central nervous tissue, adenosine, acting via at least two Ž major classes of adenosine receptors, A and A Van 1 2 . Calker et al., 1975; Londos et al., 1980 , modulates many Ž physiological functions Phillis et al., 1975; Snyder, 1985; . Durcan and Morgan, 1989; Phillis, 1990 . Activation of adenosine A receptors inhibits adenylyl cyclase and 1 thereby reduces cyclic AMP formation, while activation of Ž adenosine A receptors has the opposite effect Fredholm 2 et al., 1982; Dunwiddie and Fredholm, 1989; Lupica et al., . 1990 . In hippocampal neurons, endogenous adenosine and its derivatives, acting via adenosine A andror A recep- 1 2 tors, are therefore considered to be involved in the mecha- nism of the frequency-dependent synaptic plasticity, such as long-term potentiation and depotentiation of long-term potentiation. Ž . Arai et al. 1990 have reported that adenosine, acting 0014-2999r97r$17.00 q 1997 Elsevier Science B.V. All rights reserved. Ž . PII S0014-2999 97 01024-8