Ketamine increases striatal dopamine release and hyperlocomotion in adult rats after postnatal functional blockade of the prefrontal cortex

Our study provides an anatomo-functional framework that may contribute toward a better understanding of the involvement of NMDA glutamatergic receptors in schizophrenia

Y. Usun

2013

Scholarcy highlights

  • Schizophrenia is a complex and devastating neuropsychiatric disorder that may result from defective connectivity between several integrative brain regions,
  • Compared to PBS animals, in rats microinjected with TTX, ketamine challenge induced a greater release of dopamine in the dorsal striatum for the highest dose and the intermediate dose
  • Our study provides an anatomo-functional framework that may contribute toward a better understanding of the involvement of NMDA glutamatergic receptors in schizophrenia
  • Data obtained during the present study showed that after administration of ketamine, the two indexes were higher in TTX animals than PBS animals, the suggestion being that animals microinjected with TTX in the left SUB at postnatal day 8 present greater reactivity to ketamine than animals microinjected with PBS
  • Ketamine is an NMDA receptor channel blocker that is used by humans for both licit and illicit purposes.In animal studies, ketamine produces anesthetic effects at high doses, while stimulating locomotor activity at lower doses.For example, rats and mice injected with a moderate dose of ketamine often exhibit an initial period of hypoactivity, lasting for up to 30 min, and a prolonged period of hyperactivity
  • Our study showed that chronic unpredictable stress induced a significant depression-like behavior accompanied by an upregulation of Early growth response 1 and downregulations of PSD-95, spine density, and AMPAR currents in the hippocampus, and a single dose of ketamine rapidly restored these changes
  • The purpose of the present study was threefold: first, to measure the locomotor activating effects of ketamine in male and female rats across early ontogeny and into adulthood; second, to assess ketamine and norketamine pharmacokinetics in the dorsal striatum and hippocampus of the same age groups; and, third, to use curvilinear regression to determine the relationship between locomotor activity and dorsal striatal concentrations of ketamine and norketamine

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