Table 3. Summary of the behaviors, physiological responses, and neural circuits for the actions of ketamine (NMDA receptor antagonist)^a.

Drugs	Behavioral and physiological responses	Possible neural circuit mechanisms	Receptors
Ketamine	Analgesia	Blockade of NMDA-mediated nociceptive stimuli in the dorsal horn of the spinal cord	NMDA
	Dissociative state hallucinations	Preferential binding to NMDA receptors on GABAergic inhibitory interneurons in cerebral cortex, hippocampus, and limbic structures, resulting in disinhibition and aberrant excitatory activity in these areas. Hallucinations are treated with benzodiazepines, which is consistent with a GABA-mediated mechanism
	Antidepressant effect	Increased neurogenesis and synaptogenesisChange in the NMDA to AMPA receptor activity ratioNMDA-mediated cortical activation by inhibition of GABAergic inhibitory interneurons (chemical ECT induced by disinhibition)
	Lacrimation and salivation	Increased parasympathetic stimulation of inferior and superior salivatory nuclei due to NMDA-mediated inhibition of GABAergic interneurons (disinhibition)
	Pupillary dilation, tachycardia, bronchodilation	Increased sympathetic output from nucleus tractus solitarius due to NMDA-mediated inhibition of GABAergic interneurons (disinhibition)
	Nystagmus	Increased activity in cortical areas generating saccades (disinhibition via NMDA inhibition of GABA interneurons) combined with decreased activity in cerebellum and brain stem reticular formation and medial vestibular nuclei (direct inhibition of NMDA neurons)

^aAbbreviations: AMPA, 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid; ECT, electroconvulsive therapy; GABA_A, gamma aminobutyric acid type A; NMDA: N-methyl D-aspartate.