Early Prefrontal Functional Blockade in Rats Results in Schizophrenia-Related Anomalies in Behavior and Dopamine

Autor: Francisca Meyer, Alain Louilot
Přispěvatelé: Faculty of Medicine-ULP
Rok vydání: 2012
Předmět:
Male
Dextroamphetamine
[SDV]Life Sciences [q-bio]
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Dopamine
Prefrontal Cortex
Tetrodotoxin
Motor Activity
Nucleus accumbens
Nucleus Accumbens
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Latent inhibition
Neurochemical
Dopamine Uptake Inhibitors
medicine
Animals
Prefrontal cortex
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
Pharmacology
0303 health sciences
[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior
Dopaminergic
Neural Inhibition
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
medicine.disease
Rats
Disease Models
Animal
Inhibition
Psychological
Psychiatry and Mental health
Animals
Newborn
chemistry
Schizophrenia
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Original Article
Psychology
Neuroscience
030217 neurology & neurosurgery
Sodium Channel Blockers
medicine.drug
Zdroj: Neuropsychopharmacology
Neuropsychopharmacology, Nature Publishing Group, 2012, 37 (10), pp.2233-2243. ⟨10.1038/npp.2012.74⟩
ISSN: 1740-634X
0893-133X
0007-0920
DOI: 10.1038/npp.2012.74
Popis: Growing evidence suggests schizophrenia may arise from abnormalities in early brain development. The prefrontal cortex (PFC) stands out as one of the main regions affected in schizophrenia. Latent inhibition, an interesting cognitive marker for schizophrenia, has been found in some studies to be reduced in acute patients. It is generally widely accepted that there is a dopaminergic dysfunctioning in schizophrenia. Moreover, several authors have reported that the psychostimulant, D-amphetamine (D-AMP), exacerbates symptoms in patients with schizophrenia. We explored in rats the effects in adulthood of neonatal transient inactivation of the PFC on behavioral and neurochemical anomalies associated with schizophrenia. Following tetrodotoxin (TTX) inactivation of the left PFC at postnatal day 8, latent inhibition-related dopaminergic responses and dopaminergic reactivity to D-AMP were monitored using in vivo voltammetry in the left core part of the nucleus accumbens in adult freely moving rats. Dopaminergic responses and behavioral responses were followed in parallel. Prefrontal neonatal inactivation resulted in disrupted behavioral responses of latent inhibition and latent inhibition-related dopaminergic responses in the core subregion. After D-AMP challenge, the highest dose (1.5 mg/kg i.p.) induced a greater dopamine increase in the core in rats microinjected with TTX, and a parallel increase in locomotor activity, suggesting that following prefrontal neonatal TTX inactivation animals display a greater behavioral and dopaminergic reactivity to D-AMP. Transitory inactivation of the PFC early in the postnatal developmental period leads to behavioral and neurochemical changes in adulthood that are meaningful for schizophrenia modeling. The data obtained may help our understanding of the pathophysiology of this disabling disorder.
Databáze: OpenAIRE
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