Impulsive behaviour in rats induced by intracortical DOI infusions is antagonized by co-administration of an mGlu2/3 receptor agonist

Behav Pharmacol. 2011 Dec;22(8):805-13. doi: 10.1097/FBP.0b013e32834d6279.

Abstract

The orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC) modulate impulsive behaviours. Serotonin [5-hydroxytryptamine (5-HT)] 2A receptors have also been implicated in impulsivity and govern antagonistic interactions with metabotropic glutamate (mGlu)2/3 receptors. This study examined the interactions between 5-HT2A and mGlu2/3 receptors in the OFC and mPFC with relevance to impulsive choice and impulsive action. Impulsive choice was assessed in Lister Hooded rats, trained in a delay-discounting T-maze task, after bilateral intra-OFC infusions of the 5-HT2A/C receptor agonist DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride; 5 μg/0.5 μl] and the mGlu2/3 receptor agonist LY379268 (1 μg/0.5 μl). Impulsive action was assessed in a second group of rats trained in a five-choice serial reaction time task (5-CSRTT) and receiving bilateral intra-mPFC infusions of DOI (5 μg/0.5 μl) and LY379268 (1 μg/0.5 μl). Intra-OFC DOI increased impulsive choice, which was not seen when DOI was co-administered with LY379268. LY379268 itself had no effect on choice behaviour. Intra-mPFC DOI caused impulsive over-responding in the 5-CSRTT that was attenuated when DOI and LY379268 were co-injected. Local mPFC-infusions of LY379268 had no effect on 5-CSRTT performance. This study suggests a differential involvement of OFC and mPFC 5-HT2A receptors in impulsive choice and impulsive action. Moreover, compounds acting at mGlu2/3 receptors might have the potential to improve impulsivity-related impairments.

MeSH terms

  • Amino Acids / pharmacology
  • Amino Acids / therapeutic use*
  • Amphetamines*
  • Animals
  • Behavior, Animal / drug effects*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use*
  • Choice Behavior / drug effects
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Agonists / therapeutic use*
  • Impulsive Behavior / chemically induced
  • Impulsive Behavior / drug therapy*
  • Prefrontal Cortex / drug effects
  • Rats
  • Reaction Time / drug effects
  • Receptors, Metabotropic Glutamate / agonists*

Substances

  • Amino Acids
  • Amphetamines
  • Bridged Bicyclo Compounds, Heterocyclic
  • Excitatory Amino Acid Agonists
  • LY 379268
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • 4-iodo-2,5-dimethoxyphenylisopropylamine