Activation of postsynaptic D2 dopamine receptors in the rat dorsolateral striatum prevents the amnestic effect of systemically administered neuroleptics

Behav Brain Res. 2015 Mar 15:281:283-9. doi: 10.1016/j.bbr.2014.12.040. Epub 2014 Dec 26.

Abstract

Systemically administered antipsychotics bind to dopamine (DA) D2 receptors expressed in both pre- and postsynaptic neurons of different striatal sites and present an amnestic effect on learning and memory of conditioned avoidance responses (CAR). The aim of this study was to test whether blockade of the pre- or post-synaptic D2 receptors of the dorsolateral striatum of rats is the mechanism by which systemically administered antipsychotics present this amnestic effect. CAR learning and memory was evaluated in rats that received i.p. administrations of pre- or postsynaptic doses of the antipsychotic sulpiride combined with intra-DLS infusion of the D2 agonist quinpirole. Intra-DLS quinpirole itself was not amnestic and this effect was prevented by co-administration of presynaptic dose of sulpiride. However, sulpiride was amnestic when administered systemically in a post- but not presynaptic dose. This amnestic effect of sulpiride was prevented by the co-administration of quinpirole into the DLS. These results show that a blockade of postsynaptic D2 receptors in the DLS is necessary and sufficient to produce the amnestic effect of neuroleptics on CARs.

Keywords: Action-selection; Basal ganglia; Neuroleptic; Schizophrenia; Two-way active avoidance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / pharmacology*
  • Avoidance Learning / drug effects
  • Conditioning, Operant / drug effects
  • Corpus Striatum / drug effects*
  • Dopamine D2 Receptor Antagonists / pharmacology*
  • Drug Therapy, Combination
  • Male
  • Memory / drug effects*
  • Neurons / drug effects
  • Quinpirole / administration & dosage
  • Quinpirole / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / agonists*
  • Receptors, Dopamine D2 / metabolism*
  • Sulpiride / administration & dosage
  • Sulpiride / pharmacology
  • Synaptic Membranes / drug effects

Substances

  • Antipsychotic Agents
  • Dopamine D2 Receptor Antagonists
  • Receptors, Dopamine D2
  • Quinpirole
  • Sulpiride