Administration of either non-NMDA receptor agonists or NMDA receptor antagonists into the substantia nigra or the globus pallidus reduces the psychostimulant effect of high helium pressure on locomotor activity in rats

HELIUM pressure of > 2 MPa is a well known factor underlying pressure-depen dent central neuroexcitatory disorders that include locomotor and motor act ivity (LMA) and myoclonia. We investigated the effects of bilateral injecti on in either the substantia nigra (SN) or the globus pallidus (GP) of the A MPA receptor agonist (+/-) AMPA, the kainate receptor agonist kainic acid, the NMDA receptor agonist (+/-)-cis-piperidine-2,3-dicarboxylic acid (PDA), and the NMDA receptor antagonist (+/-)-2-amino-7-phosphono-heptanoic acid (AP-7) in the occurrence of helium pressure-induced LMA and myoclonia. Admi nistration of AMPA, kainate, or AP-7 in either the SN or the GP significant ly reduced high helium pressure-induced LMA, whereas the NMDA receptor agon ist showed no significant effect. Injection in the SN of the non-NMDA recep tor agonist AMPA and the NMDA receptor agonist PDA increased the developmen t of high helium pressure-induced myoclonia, whereas injection of the NMDA receptor antagonist AP-7 into the SN or the GP decreased it. This confirms that NMDA transmission in the SN and the GP would play a major role in the development of helium pressure-induced LMA; manipulation of AMPA and kainat e systems may have therapeutic potential. The opposite effects of AMPA on L MA and myoclonia also confirm the neural substrates involved in the motor d isorder produced by helium pressure differ substantially between LMA and my oclonia. (C) 1999 Lippincott Williams & Wilkins.