Effects of morphine-3-glucuronide and morphine on the K+-evoked release of [H-3]-glutamic acid and [C-14]-gamma-aminobutyric acid from rat brain synaptosomes

The effects of morphine-3-glucuronide (M3G) and morphine on the K+-evoked release of [C-14]-gamma-aminobutyric acid (GABA) and [(3)]-glutamic acid were investigated in rat brain synaptosome using superfusion techniques. K+-evoked release of both [C-14]-GABA and [H-3]-glutamic acid from rat brain synaptosomes was eliminated in the absence of calcium, indicating that K+-evoked neurotransmitter release was from vesicular stores in a manner analagous to that which occurs in vivo following an action potential (1). Addition of M3G or morphine in a range of concentrations (0.1 - 10 mu M) to the superfusion medium did not alter the K+-evoked release of [C-14]-GABA or [H-3]-glutamic acid from rat brain synaptosomes, suggesting that the CNS excitation observed following central administration of M3G (2-5) and supra-analgesic doses of morphine (2,3,6,7) does not occur by a generalized inhibition of GABA release or facilitation of glutamic acid release from pre-synaptic nerve terminals.