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Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
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Mutant DISC1 affects methamphetamine-induced sensitization and conditioned place preference: a comorbidity model.

Vladimir M Pogorelov1, Jun Nomura, Jongho Kim

  • 1Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 8-121, Baltimore, MD 21287, USA.

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Genetic variants in DISC1 impact neurobehavioral responses to methamphetamine (METH) in female mice. This suggests DISC1

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Genetic factors influencing neuroplasticity are linked to psychiatric disorders.
  • The Disrupted-In-Schizophrenia-1 (DISC1) gene's interactome suggests a role in addiction and mental illness.

Purpose of the Study:

  • To investigate how a dominant-negative mutant DISC1 affects neurobehavioral and molecular responses to methamphetamine (METH).
  • To explore the role of DISC1 in the ventral striatum concerning METH-induced reward and sensitization.

Main Methods:

  • Utilized control and mutant DISC1 mice, studying them before and after escalating doses (ED) of METH.
  • Assessed METH-induced conditioned place preference (CPP), dopamine D2 receptor density, and AKT/GSK-3β activity.
  • Evaluated fear conditioning, depression-like behaviors, and drug-induced molecular changes post-METH treatment.

Main Results:

  • Naïve mutant DISC1 female mice showed impaired METH-induced CPP, reduced dopamine D2 receptor density, and altered AKT/GSK-3β phosphorylation.
  • Methamphetamine ED regimen was not neurotoxic.
  • Mutant DISC1 delayed METH ED-produced sensitization and affected drug-induced AKT/GSK-3β phosphorylation in female mice.

Conclusions:

  • DISC1 dysfunction in the ventral striatum may influence reward and sensitization pathways.
  • These findings suggest a potential link between DISC1 perturbations, drug abuse, and the comorbidity of mental diseases.