Hyperactivity following injection of a glutamate agonist and 6,7-ADTN into rat nucleus accumbens and its inhibition by THIP

The potent glutamate receptor agonist AMPA induced a dose related hyperactivity after bilateral injection of 0.025–0.5 μg into rat nucleus accumbens. The dopamine agonist 6, 7-ADTN (2.5–10 μg) induced a similar effect. The hyperactivity induced by AMPA and 6, 7-ADTN was antagonized by cis-Z-flupentixol (0.31 mg/kg). Reserpine (7.5 mg/kg) plus α-methyltyrosine (200 mg/kg) inhibited AMPA but not 6, 7-ADTN induced motility. Furthermore, AMPA and 6, 7-ADTN induced motility was antagonized by the GABA agonist THIP after systemic administration (5 mg/kg) and intraaccumbens injection (0.125–0.5 μg). The results suggest that glutamatergic mechanisms are important in regulation of locomotor activity by influencing mechanisms afferent to dopamine receptors. Both glutamate and dopamine systems are under inhibitory GABAergic control.