Multi-dimensional analyses of behavior in mice treated with U-50,488H, a purported kappa (non-mu) opioid agonist

The effects of U-50, 488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl ]-benzeneacetamide, methane sulfonate, hydrate), a purported selective kappa (non-mu) opioid agonist on spontaneous locomotor activity were investigated using a multi-dimensional behavioral analyzer (Animex II). U-50,488H (1 mg/kg) failed to affect behavior in mice, however, 3 mg/kg significantly reduced rearing and grooming. In addition, 10 mg/kg markedly reduced linear locomotion, rearing and grooming. The behavioral depression induced by U-50,488H (10 mg/kg) was reversible by the opioid antagonist Mr2266 (10 mg/kg). These results suggest that the selective activation of the kappa (non-mu) opioid receptor by U-50,488H decreases linear locomotion, rearing and grooming in mice.