High helium pressure of more than 2 MPa produces central neuroexcitatory motor behavior. In rodents, symptoms comprise locomotor and motor activity (LMA), myoclonia, and, at pressure greater than 9-10 MPa, convulsions and tonic-clonic seizures. We studied the behavioral effects of bilateral injection of the glutamate uptake inhibitor L-trans-pyrollidine-2,4-dicarboxylic acid (L-trans-PDC), in either the substantia nigra reticulata (SNr), the globus pallidus (GP), or the striatum on high helium pressure-induced LMA and myoclonia. Injection of L-trans-PDC in the GP and the SNr attenuated LMA, whereas injection in the striatum enhanced it. Alternatively, injection of L-trans-PDC in the SNr increased myoclonia, whereas injection in the GP or the striatum showed no effects on myoclonia. These results confirm that helium pressure-induced LMA and myoclonia have different neural origins. According to current thinking on basal ganglia function and previous data, it is suggested that high helium pressure would lead to a reduction of glutamate transmission in the SNr that could contribute to a reduction in activity of the nigrothalamic GABA pathway and then to the occurrence of LMA. It is further suggested that glutamate and DA transmissions in the striatum could have synergistic, rather than antagonistic, influences on motor activity.