Altered behavioral responses mediated by serotonin receptors in the genetically dystonic (dt) rat.

The genetically dystonic (dt) rat is an animal model of dystonia that displays sustained abnormal movements that include: torticollis, clasping of the hindlimbs, rigidity of the limbs, and contortions of the trunk. Since serotonin (5-HT) has been shown to be involved in some animal models of movement disorders, the functional responsiveness of the 5-HT system in dt rats and phenotypical normal littermates was examined by administering 5-HT agonists selective for different receptor subtypes and observing behavioral responses associated with the activation of specific 5-HT receptor subtypes. The dt rats were 6-fold more sensitive to the ability of the 5-HT1A agonist 8-OH-2-(di-n-propylamino)tetralin (8-OH-DPAT) to produce the 5-HT behavioral syndrome. The dt rats demonstrated a diminished head-shaking response following administration of the 5-HT2 agonist 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB). However, the dt rats also displayed significantly fewer head shakes following mechanical stimulation of the aural pinnae. The inability of the dt rats to demonstrate head-shaking behavior following stimulation of 5-HT2 receptors is probably due to the dt rat's difficulty in producing the motor responses involved in this behavioral response and do not reflect alterations in 5-HT2 receptor sensitivity. These results suggest that the 5-HT system, particularly 5-HT1A receptors, may have an integral role in the abnormal movements displayed by the genetically dystonic rat and movement disorders in general.