THE EFFECT OF OMEGA-CONOTOXIN GVIA ON SYNAPTIC TRANSMISSION WITHIN THE NUCLEUS-ACCUMBENS AND HIPPOCAMPUS OF THE RAT INVITRO

1 The actions of two calcium channel antagonists, the N-channel blocker omega-conotoxin GVIA (omega-CgTx) and the L-channel antagonist nisoldipine, on synaptic transmission were investigated in the hippocampus and nucleus accumbens of the rat in vitro. 2 Omega-CgTx (100 nM for 10 min) produced a marked and irreversible reduction of focally evoked population spikes and intracellularly recorded excitatory postsynaptic potentials (e.p.s.ps) in the nucleus accumbens, which could not be overcome by increasing the stimulus strength. 3 Nisoldipine (10-mu-M for 10 min) had no effect on population spikes in the nucleus accumbens or the CA1 of the hippocampus. 4 In the hippocampus, population spikes were not irreversibly reduced by omega-CgTx (100 nM for 10 min) but rather, multiple population spikes were produced along with spontaneous synchronous discharges. This indicated that inhibitory synaptic transmission was being preferentially reduced. 5 Intracellular recordings demonstrated that omega-CgTx powerfully reduced inhibitory synaptic transmission in an irreversible manner and that excitatory transmission was also reduced but to a lesser extent. Unlike excitatory transmission in the nucleus accumbens and inhibitory transmission in the hippocampus, increasing the stimulus strength overcame the reduction of hippocampal excitatory transmission. 6 It is concluded that omega-CgTx-sensitive calcium channels are involved in the calcium entry that precedes the synaptic transmission in all these synapses. The apparent lower sensitivity of the hippocampal excitatory fibres to omega-CgTx may indicate that calcium entry that promotes transmitter release at central synapses may be mediated by pharmacologically distinct calcium channels.