DIFFERENTIAL MODULATION BY MUSCIMOL AND BACLOFEN ON ANTINOCICEPTION INDUCED BY MORPHINE, BETA-ENDORPHIN, D-PEN(2,5)-ENKEPHALIN AND U50,488HADMINISTERED INTRACEREBROVENTRICULARLY IN THE MOUSE

The present study was designed to investigate the modulatory effects o f stimulation of GABA(A) and GABA(B) receptors at supraspinal sites on antinociception induced by supraspinally administered mu-,epsilon-,de lta-, and kappa-opioid receptor agonists. The effects of the GABA(A) a nd GABA(B) receptor agonists, muscimol and baclofen respectively, on t he antinociception induced by morphine (a mu-receptor agonist), beta-e ndorphin (an epsilon-receptor agonist), D-Pen(2'5)-enkephalin (DPDPE, a delta-receptor agonist) and U50,488H -dichloroN-methyl-N-[2-(1-pyrro lidinyl)cyclohexyl] benzeocetamide); a kappa-receptor agonist) injecte d intracerebroventricularly (i.c.v.) were studied. The antinociception was assayed using the tail-flick and hot-plate tests. Muscimol at dos es of 25-200 ng, administered i.c.v. alone did not affect the latencie s of tail-flick and hot-plate thresholds, but attenuated dose-dependen tly the inhibition of the tail-flick and hot-plate responses induced b y i.c.v. administered morphine (2 mu g). beta-endorphin (1 mu g), DPDP E (10 mu g), and U50,488H (60 mu g). Baclofen (1.25-10 ng) administere d i.c.v. alone did not affect the latencies of the tail-flick and hot- plate responses, but attenuated dose-dependently the inhibition of the tail-flick and hot-plate responses induced by beta-endorphin and U50, 488H, without affecting morphine- or DPDPE-induced responses, Our resu lts indicate that activation of GABA(A) receptors at the supraspinal s ites by i.c.v. injection of muscimol antagonizes antinociception induc ed by supraspinally administered mu-,epsilon-,delta-, and kappa-opioid receptor agonists. On the other hand, activation of GABA(B) receptors at supraspinal sites by i.c.v. baclofen antagonizes antinociception i nduced by i.c.v. administered epsilon- and kappa-opioid agonists, but not mu- or delta-opioid agonists.