A role played by sigma receptors in the conditioned suppression of motility in mice

Mice exhibited marked suppression of motility (conditioned suppression) when placed in the same environment in which they had previously received an electric foot-shock. The conditioned suppression was attenuated by cyclazocine and N-allylnormetazocine (SKF-10047), sigma agonists. The effect of these drugs was reduced by chronic pretreatment with cyclazocine. This behavioral change was related to the change in binding activity of [³H]-phencyclidine to sigma receptors (defined using non-radioactive SKF-10047). In the chronic vehicle-pretreated conditioned suppression group, the K_d and B_max values of [³H]-phencyclidine binding at the high affinity site were increased when compared to those in the chronic vehicle-pretreated control group. The increased values were restored to the control levels by acute treatment with cyclazocine and SKF-10047. On the other hand, in the chronic cyclazocine-pretreated conditioned suppression group, acute cyclazocine and SKF-10047 treatment failed to change the increased values of K_d and B_max at the high affinity site. The present behavioral and receptor-binding experiments suggest that the activation of nervous system mediated by sigma receptors may be responsible for the attenuation of conditioned suppression of motility.