Baclofen and morphine analgesia in mice: GABA System mediated response

BALERIO GRACIELA N., RUBIO MODESTO C.

Buenos Aires

Congreso; VI World Conference on Clinical Pharmacology & Therapeutics; 1996

BACLOFEN AND MORPHINE ANALGESIA IN MICE: GABA SYSTEM MEDIATED RESPONSE G. N. Balerio and M. C. Rubio. Cátedra de Farmacología. Fac. de Farmacia y Bioquímica (UBA) e ININFA. Junín 956 5º piso, 1113, Buenos Aires, República Argentina.   g -aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system (CNS) is implicated in several neurological and psychological disorders. Baclofen is a selective GABA B agonist and is demonstrated to produce catatonic, hypothermia, antidepresant and analgesic effects. In previous reports we have demonstrated a dose-related antinociceptive effect of baclofen (BAC) administered intraperitoneally (i.p.) to mice by hot- plate (HP). The analgesic effect of drugs was measured 1h post-administration. The DE50 value of BAC was approximately 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 (43+4.1%) was added with that effect (75+9.9%). The administration of GABA 50 and 100mg/Kg i.p. produced analgesia similar to that caused by baclofen, (30-70% respectively). The aim of this study was to investigate the participation of GABAergic pathways within the central nervous system in baclofen and morphine induced analgesia . The analgesic effect of BAC was sensitive to reversal by 2-OH-saclofen 3mg/Kg i.p. (27+3.5%) and 0.3mg/Kg intracisternally (i.c.m.)  (-2.18+3.4%) 10min before BAC. The analgesic effect of morphine was also reversed by 2-OH-saclofen 0.3mg/Kg i.c.m.(5+3%).  On the other hand the i.c.m. administration of the inhibitor of GABA- transaminase activity ethanolamine o-sulphate (EOS) 2mg/Kg 2h before morphine potentiated the analgesic effect (84+2.4%). In conclusion, the results of this study indicate that GABAB receptors are involved in baclofen analgesia. As the EOS potentiated morphine induced analgesia and 2-OH-saclofen antagonized this effect, it would suggest a role for GABA in this analgesia. The synergism between morphine and baclofen and the reversal of morphine analgesia by 2-OH-saclofen would indicate a possible cooperativity between GABAergic and opioidergic systems in the production of analgesia.