Effects of NMDA antagonism on striatal dopamine release in healthy subjects: Application of a novel PET approach

✍ Scribed by Alan Breier; Caleb M. Adler; Neil Weisenfeld; Tung-Ping Su; Igor Elman; Lisa Picken; Anil K. Malhotra; David Pickar

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 68 KB
• Volume: 29
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199806)29:2<142::aid-syn5>3.0.co;2-7

✦ Synopsis

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 Ϯ SD) in specific 11 C-raclopride binding from baseline for ketamine (11.2 Ϯ 8.9) was greater than for saline (1.9 Ϯ 3.7) (t ϭ 2.4, df ϭ 13, P ϭ 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 Ϯ SD) in specific 11 C-raclopride binding caused by amphetamine (15.5 Ϯ 6.2) (t ϭ 1.3, df ϭ 19, P ϭ 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.