AMPA glutamate receptor activation in the posterior zona incerta inhibits amphetamine- and apomorphine-induced stereotypy.

Previous work demonstrated that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor antagonism in the zona incerta (ZI) dorsal to the subthalamic nucleus inhibits stereotypy in rats. The current investigation was undertaken to determine if AMPA receptors in a more caudal portion of the ZI have a role in the expression of stereotyped behavior. Rats were injected bilaterally with AMPA into the posterior ZI dorsal to the substantia nigra, and immediately given a systemic injection of d-amphetamine (10 mg/kg, s.c.) or apomorphine (1 mg/kg s.c.). AMPA produced a dose-dependent inhibition of stereotypy induced by both drugs which was prevented by the coadministration of the AMPA/kainic acid antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX) (0.5 microgram/0.5 microliter). A dose of AMPA as low as 62.5 ng completely abolished the oral component of stereotypy induced by both apomorphine and amphetamine. This dose of AMPA alone had no significant effect on spontaneous locomotor activity but enhanced the locomotor response stimulated by amphetamine (10 mg/kg, s.c.) due to an inhibition of stereotypy. The finding that activation of AMPA receptors in the posterior ZI inhibits stereotypy shows a contrast to results in the neighboring medial ZI dorsal to the subthalamic nucleus, where blockade of AMPA/kainic acid glutamate receptors with DNQX inhibits stereotypy.