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 Kd and Bmax 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 Kd and Bmax 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.
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