Effects of antipsychotic D2 antagonists on long-term potentiation in animals and implications for human studies

Prog Neuropsychopharmacol Biol Psychiatry. 2014 Oct 3:54:83-91. doi: 10.1016/j.pnpbp.2014.05.001. Epub 2014 May 10.

Abstract

In people with schizophrenia, cognitive abilities - including memory - are strongly associated with functional outcome. Long-term potentiation (LTP) is a form of neuroplasticity that is believed to be the physiological basis for memory. It has been postulated that antipsychotic medication can impair long-term potentiation and cognition by altering dopaminergic transmission. Thus, a systematic review was performed in order to assess the relationship between antipsychotics and D2 antagonists on long-term potentiation. The majority of studies on LTP and antipsychotics have found that acute administration of antipsychotics was associated with impairments in LTP in wild-type animals. In contrast, chronic administration and acute antipsychotics in animal models of schizophrenia were not. Typical and atypical antipsychotics and other D2 antagonists behaved similarly, with the exception of clozapine and olanzapine. Clozapine caused potentiation independent of tetanization, while olanzapine facilitated tetanus-induced potentiation. These studies are limited in their ability to model the effects of antipsychotics in patients with schizophrenia as they were largely performed in wild-type animals as opposed to humans with schizophrenia, and assessed after acute rather than chronic treatment. Further studies using patients with schizophrenia receiving chronic antipsychotic treatment are needed to better understand the effects of these medications in this population.

Keywords: Animals; Antipsychotics; D2; Humans; LTP; Neurophysiology.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Dopamine / metabolism
  • Dopamine D2 Receptor Antagonists / pharmacology*
  • Dopamine D2 Receptor Antagonists / therapeutic use
  • Humans
  • Long-Term Potentiation / drug effects*
  • Long-Term Potentiation / physiology
  • Schizophrenia / drug therapy

Substances

  • Antipsychotic Agents
  • Dopamine D2 Receptor Antagonists
  • Dopamine