[Effects of a subanaesthetic dose of ketamine on emotional and behavioral state in healthy subjects].
Schizophrenic patients suffer from positive (delusions, hallucinations) and negative signs (social withdrawal) as well as emotional disturbance that included quantitative (blunted affect) and qualitative impairments (discordance of emotional level). Ketamine, a phencyclidine derivative, is a non competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist. In healthy subjects its administration induces some positive symptoms (perceptual distortions.), negative symptoms (emotional deficit, apathy, social withdrawal) and cognitive changes (memory impairments and perseverations) that resemble some aspects of the symptoms of schizophrenia. A double blind cross over, placebo controlled was performed in 12 normal subjects with 2 sessions separated by one week of wash-out to determine ketamine-induced effects on behavioral and emotional responses. During each session, subjects received either ketamine or placebo (saline) infusion. A subanesthetic dose of ketamine (0,5 mg/kg) was administered by constant perfusion over 60 min. Behavioral and cognitive responses were assessed using positive and negative symptoms scales (BPRS, items from SAPS and SANS), vigilance and mood visual analog scale, subjective feelings using the Addiction Research Center Inventory (ARCI) and the Profile of Mood States (POMS). Using Philippot's method, emotions were elicited by films segments which induce a diversity of predictable emotions (fear, anger, sadness, joy, disgust and neutral state) and emotional responses were assessed by the Differential Emotions Scale (DES Izard). Low dose of ketamine induced significant effects on 7-items BPRS score (positive and negative items) and significant effects on positive and negative symptoms from SANS and SAPS. This was associated with emotional blunting of visually-induced responses that resemble aspects of schizophrenic emotional impairments. Ketamine impaired ARCI subscales (benzedrine subscale, pentobarbital-chlorpromazine subscale and LSD subscale). The recent findings of ketamine's pharmacology and imaging studies allow to draw several hypothesis related to neurotransmitter systems (glutamate, dopamine, serotonin interactions) and cerebral areas (particularly prefrontal cortex, anterior cingulate cortex, hippocampus) underlying some of these ketamine-induced effects.
Micallef
J
J
CPCET et pharmacologie clinique, institut des neurosciences physiologiques et cognitives, faculté de médecine, Fre 2109 CNRS-université de la Méditerranée, assistance publique hôpitaux de Marseille, hôpital de la Timone, 13385 Marseille cedex 05, France.
Tardieu
S
S
Gentile
S
S
Fakra
E
E
Jouve
E
E
Sambuc
R
R
Blin
O
O
D000328:Adult; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D001519:Behavior / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced; D011569:Psychiatric Status Rating Scales; D011594:Psychometrics; D012565:Schizophrenic Psychology; D019966:Substance-Related Disorders / Q000523:psychology
D000778:Anesthetics, Dissociative; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine