Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice.
It has been previously suggested that oxytocin (Oxt) may act as a natural antipsychotic. To test this hypothesis, we investigated whether disruption of the oxytocin gene (Oxt-/-) made mice more susceptible to the psychosis-related effects of amphetamine (Amp), apomorphine (Apo) and phencyclidine (PCP). We examined drug-induced changes in the prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating deficits characteristic of several psychiatric and neurological disorders, including schizophrenia. We found that treatment with Amp, Apo and PCP all had effects on PPI. However, in Oxt-/- mice, but not Oxt+/+ mice, PCP treatment resulted in large PPI deficits. As PCP is a noncompetitive N-methyl-D-aspartic acid receptor antagonist, these findings suggest that the absence of Oxt alters the glutamatergic component of the PPI.
Caldwell
H K
HK
Section on Neural Gene Expression, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-4483, USA.
Stephens
S L
SL
Young
W S
WS
D000161:Acoustic Stimulation / Q000379:methods; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics*; D010121:Oxytocin / Q000172:deficiency*; D010622:Phencyclidine / Q000494:pharmacology; D011571:Psychoacoustics; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics*; D055139:Sensory Gating / Q000187:drug effects / Q000235:genetics*; D012737:Sex Factors
D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D010121:Oxytocin; D000661:Amphetamine; D010622:Phencyclidine; D001058:Apomorphine