Baclofen modifies via the release of monoamines the synaptic depression, frequency facilitation, and posttetanic potentiation observed at an identified cholinergic synapse of Aplysia californica

1. The mechanism of action of baclofen was studied at a cholinergic synapse of Aplysia. This synapse, called RC1-R15, can be activated by a minimal stimulation of the right pleurovisceral connective and is recorded in cell R15 of Aplysia californica. Repeated stimulation of synapse RC1-R15 produces depression, followed by frequency facilitation and by posttetanic potentiation (PTP). 2. Perfusion with baclofen (3 x 10(-5) or 5 x 10(-5) M) reduces the size of all excitatory postsynaptic potentials (EPSPs) of synapse RC1-R15 produced by a train of 100 stimuli at 1.5 Hz. It also reduces the synaptic depression and PTP but increases the frequency facilitation. These effects are similar to those produced by gamma-aminobutyric acid (GABA), serotonin, and dopamine on this synapse. 3. When the preparation is perfused with bicuculline or picrotoxin, two antagonists of GABA, the effects of baclofen are not antagonized. However, when baclofen is perfused in the presence of SQ10,631 (an antagonist of serotonin) or butaclamol (an antagonist of dopamine), its effects are partially blocked. 4. To determine if baclofen produces its action by direct interaction with aminergic receptors or by liberating the amines from some nerve endings, a few animals were treated with reserpine to deplete the aminergic pool. Following this treatment no effects were obtained with baclofen suggesting that it acts by liberating dopamine and serotonin or some other amines. 5. In animals treated with reserpine, GABA still produces its normal effects (reduction of EPSP size, synaptic depression, posttetanic potentiation, and increase of facilitation), indicating that baclofen does not act directly on the GABA receptor located on the presynaptic terminal.