Crack cocaine inhalation induces schizophrenia-like symptoms and molecular alterations in mice prefrontal cortex

J Psychiatr Res. 2017 Aug;91:57-63. doi: 10.1016/j.jpsychires.2017.03.005. Epub 2017 Mar 6.


Crack cocaine (crack) addiction represents a major social and health burden, especially seeing as users are more prone to engage in criminal and violent acts. Crack users show a higher prevalence of psychiatric comorbidities - particularly antisocial personality disorders - when compared to powder cocaine users. They also develop cognitive deficits related mainly to executive functions, including working memory. It is noteworthy that stimulant drugs can induce psychotic states, which appear to mimic some symptoms of schizophrenia among users. Social withdraw and executive function deficits are, respectively, negative and cognitive symptoms of schizophrenia mediated by reduced dopamine (DA) tone in the prefrontal cortex (PFC) of patients. That could be explained by an increased expression of D2R short isoform (D2S) in the PFC of such patients and/or by hypofunctioning NMDA receptors in this region. Reduced DA tone has already been described in the PFC of mice exposed to crack smoke. Therefore, it is possible that behavioral alterations presented by crack users result from molecular and biochemical neuronal alterations akin to schizophrenia. Accordingly, we found that upon crack inhalation mice have shown decreased social interaction and working memory deficits analogous to schizophrenia's symptoms, along with increased D2S/D2L expression ratio and decreased expression of NR1, NR2A and NR2B NMDA receptor subunits in the PFC. Herein we propose two possible mechanisms to explain the reduced DA tone in the PFC elicited by crack consumption in mice, bringing also the first direct evidence that crack use may result in schizophrenia-like neurochemical, molecular and behavioral alterations.

Keywords: Crack cocaine; D2 dopamine receptor; Drug addiction; NMDA receptors; Negative symptoms; Schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Crack Cocaine / toxicity*
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects*
  • Interpersonal Relations
  • Male
  • Maze Learning
  • Memory Disorders / chemically induced
  • Memory, Short-Term / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Protein Isoforms / metabolism
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Schizophrenia / chemically induced*
  • Schizophrenia / complications
  • Schizophrenia / pathology
  • Schizophrenic Psychology


  • Crack Cocaine
  • NR2B NMDA receptor
  • Protein Isoforms
  • Receptors, Dopamine D2
  • Receptors, N-Methyl-D-Aspartate