(+)-cis-Dioxolane (0.5-2 micrograms), a muscarinic receptor agonist, given intracerebroventricularly (i.c.v.) produced a dose-dependent inhibition of the tail-flick response in male ICR mice. (+)-cis-Dioxolane given i.c.v. at a subanalgesic dose (0.25 micrograms), selectively potentiated the antinociceptive response induced by i.c.v. administered beta-endorphin, an epsilon-opioid receptor agonist, but not morphine or [D-Ala2,NMePhe4,Gly5-ol]enkephalin (DAMGO), mu-opioid receptor agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE), a delta receptor agonist, or trans(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methane sulfonate (U50,488H), a kappa-opioid receptor agonist. The antinociceptive response induced by (+)-cis-dioxolane given i.c.v. was attenuated by i.c.v. treatment with N omega-nitro-L-arginine (1 microgram), hemoglobin (120 micrograms) or methylene blue (10 micrograms). The antinociception induced by carbachol given i.c.v. was also antagonized by the i.c.v. treatment with N omega-nitro-L-arginine (1 microgram). However, the same treatment with N omega-nitro-L-arginine, hemoglobin or methylene blue did not affect the beta-endorphin-induced antinociception. The potentiation of beta-endorphin-induced antinociception by (+)-cis-dioxolane was reversed by i.c.v. treatment with N omega-nitro-L-arginine (1 microgram), hemoglobin (120 micrograms) or methylene blue (10 micrograms). On the other hand, the antinociceptive response induced by (+)-cis-dioxolane (1 microgram) given i.c.v. was potentiated by i.c.v. administered L-arginine (20 micrograms) but not D-arginine (20 micrograms). Dibutyryl cyclic GMP at 0.5-2.0 micrograms given i.c.v. produced an antinociceptive response and at subanalgesic dose (0.1 microgram) potentiated i.c.v. beta-endorphin-induced antinociception.(ABSTRACT TRUNCATED AT 250 WORDS)