BEHAVIORAL AND NEUROCHEMICAL INTERACTIONS OF THE AMPA ANTAGONIST GYKI-52466 AND THE NONCOMPETITIVE NMDA ANTAGONIST DIZOCILPINE IN RATS

The behavioural and neurochemical effects of the N-methyl-D-aspartate (NMDA) antagonist dizocilpine and the lpha-amino-3-hydroxy-5-methyliso xazole-4-propionic acid (AMPA) antagonist GYKI 52466, given alone or i n combination, were investigated in rats. Locomotor activity was incre ased by dizocilpine (0.2 mg/kg), but not by GYKI 52466 (2.4 mg/kg). Di zocilpine-induced hyperlocomotion was reduced by co-administration of GYKI 52466. In dizocilpine-treated rats dopamine (DA) metabolism (meas ured as DOPAC [dihydroxyphenylacetic acid] or DOPAC/DA in post mortem brain tissue) was increased in the prefrontal cortex and nucleus accum bens. In GYKI 52466-treated rats serotonin was reduced in the prefront al cortex and nucleus accumbens while DA metabolism was not affected. In rats treated with dizocilpine plus GYKI 52466, DA metabolism was in creased only in the prefrontal cortex, but not in the nucleus accumben s, when compared with vehicle-treated animals. These data confirm that AMPA and NMDA antagonists do not have synergistic effects on locomoto r activity. A differential role of NMDA and AMPA antagonists in the co ntrol of mesolimbic DA neurons will be discussed here.