Impulsive behaviour in rats induced by intracortical DOI infusions is antagonized by co-administration of an mGlu23 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)23 receptors. This study examined the interactions between 5-HT2A and mGlu23 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-HT2AC receptor agonist DOI (-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride 5 μg0.5 μl and the mGlu23 receptor agonist LY379268 (1 μg0.5 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 μg0.5 μl) and LY379268 (1 μg0.5 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 mGlu23 receptors might have the potential to improve impulsivity-related impairments.