Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex
Journal of Neuroscience April 15, 1997 Bita Moghaddam, Barbara W. Adams, Anita Verma et al. 1,813 citations
Low doses of the NMDA receptor antagonist ketamine (10, 20, and 30 mg/kg) increase glutamate outflow in the rat prefrontal cortex (PFC), suggesting enhanced glutamatergic neurotransmission at non-NMDA receptors. An anesthetic dose (200 mg/kg) decreases glutamate levels, while an intermediate dose (50 mg/kg) has no effect. Ketamine at 30 mg/kg also increases dopamine release in the PFC, an effect blocked by intra-PFC application of the AMPA/kainate receptor antagonist CNQX. Systemic pretreatment with the AMPA/kainate receptor antagonist LY293558 ameliorates ketamine-induced dopamine release and impairment of spatial delayed alternation, a PFC-sensitive cognitive task. Ketamine may disrupt PFC dopaminergic neurotransmission and cognitive functions partly by increasing glutamate release and stimulating postsynaptic non-NMDA glutamate receptors.