Chronic administration of 1,3-di-o-tolylguanidyne induces catalepsy and reduces immobility responses by clamping and grasping in Wistar rat, evaluation in vivo and in silico.

Catalepsy, used to assess antipsychotic effects in animal models, involves sustained abnormal postures and resistance to displacement through balance reflexes. In contrast, immobility is a passive, stimulus-induced state marked by reduced movement and responsiveness, it can be triggered by a variety of stimuli. We found that a single administration of 1,3-di-o-tolylguanidine (DTG) had no effect on catalepsy, whereas daily administration induced cataleptic behavior by day 21. DTG reduced dorsal (grasping) and clamping immobility from the first day of administration, and this reduction persisted through day 21. Our findings support the potential use of sigma receptors as targets for antipsychotic drug development. Molecular dynamics studies indicate that DTG exhibits high stability and binding affinity for sigma-1 and dopamine D2 receptors, which may underlie its behavioral effects. Given the well-documented cataleptic properties of haloperidol, we compared and discussed both the molecular dynamics and previously reported behavioral effects of DTG in relation to haloperidol.