Morphine and related compounds: evidence that they decrease available neurotransmitter in Aplysia californica

Abstract

Studies were made of the action of morphine on an identified monosynaptic, unitary excitatory postsynaptic potential (EPSP) in the abdominal ganglion of Aplysia californica. The synapse is presumed to be cholinergic. Upon repetitive stimulation of the right pleurovisceral connective the size of EPSPs recorded intracellularly in cell R15 undergo a progressive depression followed by facilitation to a frequency dependent plateau and a period of post-tetanic potentiation. Perfusion with10 −4 M morphine for 3 h reduced the size of every EPSP of the train to about 50% of its control value. The relative depression, facilitation and post-tetanic potentiation (measured as a fraction of the first EPSP of a train) were not affected by morphine. The minimal effective concentration of morphine was about10 −5 M. The morphine effect on EPSP amplitude does not appear to be due to blockade of the postsynaptic receptor since the potential obtained by iontophoretic application of acetylcholine onto the postsynaptic cell body was not decreased by morphine perfusion. The effect of morphine on the EPSPs appears to be due to reduction of neurotransmitter release from the presynaptic terminal. The reduction of transmitter release seems to result from a general reduction in the supply of transmitter to the pool available for release. This contrasts with previous studies on a group of drugs typified by trimethidinium, which appear to selectively block frequency dependent supply of neurotransmitter without affecting the frequency independent supply process. Naloxone, which is an antagonist of morphine in many other systems did not antagonize the morphine effect in this system. Instead, it too decreased the amplitude of all EPSPs of a train. Levorphanol and dextrorphan also produced these effects, indicating that the ‘receptor’ for this action of opiates is not stereospecific. The relatively high concentrations of morphine required to produce the effect, and the lack of stereospecificity distinguish these findings from some actions of morphine in vertebrate preparations. However, some morphine effects in vertebrate preparations are similar to those observed here. Whereas the relationship of these findings to the analgesic action of morphine is unclear, the characteristics of its action at this synapse assist in the pharmacological analysis of regulation of transmitter release in Aplysia.