Impulsive behaviour in rats induced by intracortical DOI infusions is antagonized by co-administration of an mGlu2/3 receptor agonist.
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.
Department of Neuropharmacology, University of Bremen, Brain Research Institute, COGNIUM, Bremen, Germany. lena_wischhof@yahoo.de
Lena
L
Wischhof
Karl J
KJ
Hollensteiner
Michael
M
Koch
D000596:Amino Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000662:Amphetamines; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology / Q000627:therapeutic use*; D002755:Choice Behavior / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D007175:Impulsive Behavior / Q000139:chemically induced / Q000188:drug therapy*; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*
D000596:Amino Acids; D000662:Amphetamines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018690:Excitatory Amino Acid Agonists; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine