Vulnerability to psychotogenic effects of ketamine is associated with elevated D2/3-receptor availability.
Previous positron emission tomography (PET) studies employing competition paradigms have shown either no change or substantial declines in striatal [(11)C]-raclopride binding after challenge with psychotogenic doses of the N-methyl-D-aspartate antagonist ketamine. We sought to probe the relationship between the severity of ketamine-induced psychotic symptoms and altered dopamine D(2/3) receptor availability throughout brain using the high affinity ligand [(18)F]-fallypride (FP). PET recordings were obtained in a group of 10 healthy, young male volunteers, in a placebo condition, and in the course of an infusion with ketamine at a psychotomimetic dose. Administration of the Positive and Negative Syndrome Scale and the Thought and Language Index in both conditions revealed a substantial emergence of mainly negative symptoms of schizophrenia, persisting until the end of the 3 h PET recordings. The baseline FP binding in cortex, caudate nucleus and other brain regions was highly predictive of the individual severity of psychotic symptoms in the ketamine condition. However, there was no evidence of ketamine-evoked reductions in FP binding. In the context of earlier findings, we speculate that high baseline D(2/3)-receptor availability may impart benefits with regard to cognitive flexibility, but increases the risk of maladaptive information processing in the face of environmental stresses and challenges.
Department of Psychiatry and Psychotherapy, Medical Faculty, RWTH Aachen University, Aachen, Germany. ivernaleken@ukaachen.de
Ingo
I
Vernaleken
Majken
M
Klomp
Olaf
O
Moeller
Mardjan
M
Raptis
Arne
A
Nagels
Frank
F
Rösch
Wolfgang M
WM
Schaefer
Paul
P
Cumming
Gerhard
G
Gründer
D000328:Adult; D001549:Benzamides / Q000378:metabolism*; D005824:Genetics, Behavioral / Q000187:drug effects*; D006801:Humans; D007649:Ketamine / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis*; D050637:Receptors, Dopamine D3 / Q000096:biosynthesis*; D016037:Single-Blind Method; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D001549:Benzamides; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D007649:Ketamine; C574003:fallypride