INVESTIGADORES
BALERIO Graciela Noemi
congresos y reuniones científicas
Título:
On the involvement of GABA in the analgesia produced by baclofen and morphine
Autor/es:
BALERIO GRACIELA N., RUBIO MODESTO C.
Lugar:
Milan, Italia
Reunión:
Congreso; First European Congress of Pharmacology; 1995
Resumen:
ON THE INVOLVEMENT OF GABA IN THE ANALGESIA PRODUCED BY BACLOFEN AND MORPHINE
G. N. Balerio and M. C. Rubio
Cátedra de Farmacología.Fac. de Farmacia y Bioquímica (UBA) e ININFA (CONICET)
Junín 956 5º piso, 1113, Buenos Aires, República Argentina.
In previous reports we have demonstrated a dose-related antinociceptive effect of baclofen (BAC) administered intraperitoneally (i.p.) to mice by hot plate (HP) and the DE50 value of BAC was 2mg/kg i.p. This dose showed a percentage of the maximum possible effect (%MEP): 44 + 3 and the analgesic effect of morphine 2mg/kg (%MEP): 43 + 4.1 was added with that effect %MEP: 75 + 9.9.
The administration of GABA 50 and 100mg/kg i.p. produced analgesia similar to that caused by baclofen, being the %MEP: 30-70 respectively. It has been suggested that GABAergic mechanisms mediate the supraespinal action of BAC.
The present study was undertaken to investigate the effects of the GABA B antagonist (2-OH-saclofen) on analgesia produced by baclofen 2mg/kg i.p. and morphine 2mg/kg i.p., 1h postadministration.
Additionally we study the effect of the inhibitor of GABA-transaminase activity ethanolamine o-sulphate (EOS) on morphine induced analgesia.
The analgesia effect of BAC was sensitive to reversal by 2-OH-saclofen 3mg/kg i.p. and 0.3mg/kg intracisternally (i.c.m.) 10min before BAC and the %MEP:
BAC control: 50 + 6.9 2-OH-saclofen i.p. + BAC: 27 + 3.5
BAC control: 63 + 4.9 2-OH-saclofen i.c.m. + BAC: -2.18 + 3.4
The analgesic effect of morphine was sensitive to reversal by 2-OH-saclofen 0.3mg/kg i.p. 10min before morphine and the %MEP was:
MORPHINE control: 24 + 2.3 2-OH-saclofen i.p. + MORPHINE: 24 + 2.3
MORPHINE control: 68 + 11 2-OH-saclofen i.c.m. + MORPHINE: 5 + 3
The i.c.m. administration of EOS 2mg/kg 2h before morphine potentiated the analgesic effect: MORPHINE control: 38 + 3.4 EOS + MORPHINE: 84 + 2.4
It is possible that BAC activates GABAergic pathways within the central nervous system. Irreversible inhibitor of GABA-transaminase potentiated morphine-induced analgesia and their antagonism by 2-OH-saclofen supporting a role for GABA in this analgesia.