Cocaine- and Amphetamine-Regulated Transcript Peptide (CART) Alleviates MK-801-Induced Schizophrenic Dementia-Like Symptoms

•Acute MK-801 treatment produces hyperactivity and deficits in short-term social recognition memory in rats.•Treatment of MK-801 blocks the juvenile interaction-induced increase in CART expression in the PFC, VTA and Acb.•Intracranial CART administration reverses MK-801-induced memory deficits.•Intr...

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Bibliographic Details
Published in:Neuroscience 2018-04, Vol.375, p.94-107
Main Authors: Borkar, Chandrashekhar D., Bharne, Ashish P., Nagalakshmi, B., Sakharkar, Amul J., Subhedar, Nishikant K., Kokare, Dadasaheb M.
Format: Article
Language:English
Subjects:
Animals
Benzazepines - pharmacology
Brain - drug effects
Brain - metabolism
Brain - pathology
cocaine- and amphetamine-regulated transcript peptide
Dementia - drug therapy
Dementia - metabolism
Dementia - pathology
Disease Models, Animal
Dizocilpine Maleate
immunohistochemistry
Male
Memory - drug effects
Memory - physiology
MK-801
Motor Activity - drug effects
Motor Activity - physiology
Nerve Tissue Proteins - metabolism
Nerve Tissue Proteins - pharmacology
Neurons - drug effects
Neurons - metabolism
Neurons - pathology
Psychotropic Drugs - pharmacology
Random Allocation
Rats, Wistar
Receptors, Dopamine D1 - antagonists & inhibitors
Receptors, Dopamine D1 - metabolism
schizophrenia
Schizophrenia - drug therapy
Schizophrenia - metabolism
Schizophrenia - pathology
Schizophrenic Psychology
Social Behavior
social recognition test
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Summary:•Acute MK-801 treatment produces hyperactivity and deficits in short-term social recognition memory in rats.•Treatment of MK-801 blocks the juvenile interaction-induced increase in CART expression in the PFC, VTA and Acb.•Intracranial CART administration reverses MK-801-induced memory deficits.•Intra-PFC dopamine receptor antagonist inhibits procognitive effect of CART.•CART positively modulates the dopamine system to alleviate cognitive deficits associated with schizophrenia. Exaggerated thoughts, diminished mood and impaired cognition are the hallmarks of the schizophrenia-like condition. These symptoms are attributed to the dysregulation of dopamine and glutamate signaling in the brain. Since cocaine- and amphetamine-regulated transcript peptide (CART) modulates actions of dopamine as well as glutamate, we tested the role of this peptide in MK-801-induced schizophrenic dementia-like condition. MK-801-treated rats were allowed to interact with conspecific juvenile and tested for short-term (30-min) and long-term (24-h) social memory acquisition and recall. While MK-801 impaired the social interaction with a juvenile, the behavior was restored in CART [intracerebroventricular (icv) or intra-ventral tegmental area (VTA)] pre-treated animals. This action of CART was blocked by SCH23390 (dopamine D1 receptor antagonist) administered directly into the prefrontal cortex (PFC). Application of neuronal tracer Di-I in the PFC retrogradely labeled dopamine cells of the VTA, which in turn seem to receive CARTergic innervation. A significant increase in CARTimmunoreactivity was evidenced in the VTA, PFC and accumbens of the animals allowed to interact with a juvenile. However, MK-801 treatment attenuated the peptide expression and induced social memory deficits. The schizophrenic dementia-like symptoms following antagonism of glutamatergic receptors may be attributed to the reduced dopamine activity in the mesocortical system. We suggest that CART may, positively modulate the dopamine system to alleviate cognitive deficits associated with schizophrenia.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2018.01.056