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Two of the peptides found in the stomatogastric nervous system of the spiny lobster. Panulirus interruptus, interacted to modulate the activity of the cardiac sac motor pattern. In the isolated stomatogastric ganglion, red- pigment-concentrating hormone (RPCH), but not proctolin, activated the bursting activity in the inferior ventricular (IV) neurons that drives the cardiac sac pattern. The cardiac sac pattern normally ceased within 15 min after the end of RPCH superfusion. However, when proctolin was applied within a few minutes of that time, it was likewise able to induce cardiac sac activity. Similarly, proctolin applied together with subthreshold RPCH induced cardiac sac bursting. The amplitude of the excitatory postsynaptic potentials from the IV neurons to the cardiac sac dilator neuron CD2 (1 of the 2 major motor neurons in the cardiac sac system) was potentiated in the presence of both proctolin and RPCH. The potentiation in RPCH was much greater than in proctolin alone. However, the potentiation in proctolin after RPCH was equivalent to that recorded in RPCH alone. Although we do not yet understand the mechanisms for these interactions of the two modulators, this study provides an example of one factor that can determine the 'state' of the system that is critical in determining the effect of a modulator that is 'state dependent,' and it provides evidence for yet another level of flexibility in the motor output of this system.