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Effects of NMDA antagonism on striatal dopamine release in healthy subjects: Application of a novel PET approach
Author(s) -
Breier Alan,
Adler Caleb M.,
Weisenfeld Neil,
Su TungPing,
Elman Igor,
Picken Lisa,
Malhotra Anil K.,
Pickar David
Publication year - 1998
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199806)29:2<142::aid-syn5>3.0.co;2-7
Subject(s) - dopamine , antagonism , neuroscience , nmda receptor , psychology , pharmacology , medicine , receptor
Agents that antagonize the glutamatergic N‐methyl‐d‐aspartate (NMDA) receptor, such as phenylcyclidine (PCP) and ketamine, produce a behavioral state in healthy volunteers that resembles some aspects of schizophrenia. A dysfunction in NMDA–dopaminergic interactions has been proposed as a mechanism for these behavioral effects. In this study, we examined the effects of ketamine on striatal dopamine release in healthy human subjects with a novel 11 C‐raclopride/PET displacement paradigm and compared these effects to administration of saline and the direct‐acting dopamine agonist amphetamine. We found that the percent decreases (mean ± SD) in specific 11 C‐raclopride binding from baseline for ketamine (11.2 ± 8.9) was greater than for saline (1.9 ± 3.7) (t = 2.4, df = 13, P = 0.003) indicating that ketamine caused increases in striatal synaptic dopamine concentrations. Ketamine‐related binding changes were not significantly different than the decreases in percent change (mean ± SD) in specific 11 C‐raclopride binding caused by amphetamine (15.5 ± 6.2) (t = 1.3, df = 19, P = 0.21). Ketamine‐induced changes in 11 C‐raclopride‐specific binding were significantly correlated with induction of schizophrenia‐like symptoms. The implications of this brain imaging method for studies of schizophrenia and the mechanism of action of antipsychotic drugs are discussed. Synapse 29:142–147, 1998. Published 1998 Wiley‐Liss, Inc.