Abstract
Current data indicate that dopaminergic and glutamatergic neurotransmitter systems interact. The role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptor subtypes in modulating dopamine neurotransmission, however, remains unclear. The noncompetitive AMPA antagonists, GYKI 52466 (5-40 mg/kg) and LY300164 (1-6 mg/kg), and the competitive AMPA antagonists, LY326325 (5-80 mg/kg) and NBQX (10-80 mg/kg), were compared to the dopamine antagonist, haloperidol (0.03-1.0 mg/kg), for their ability to inhibit dopamine-mediated behaviors after i.p. administration in mice. The behavioral paradigms included amphetamine- or dizocilpine-induced hyperactivity, amphetamine-induced stereotyped sniffing, and apomorphine-induced climbing and stereotyped sniffing. All four AMPA antagonists and haloperidol attenuated amphetamine- and dizocilpine-induced hyperactivity and decreased spontaneous locomotion. Haloperidol and GYKI 52466 were more potent against amphetamine than against dizocilpine. In contrast, LY326325 was more potent against dizocilpine than against amphetamine. The hyperactivity decreases by LY300164 and NBQX were most likely due to non-specific effects on motor behavior. The AMPA antagonists and haloper...Continue Reading
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