Pre-treatment with the mGlu2/3 receptor agonist LY379268 attenuates DOI-induced impulsive responding and regional c-Fos protein expression

摘要: Overactivation of serotonin (5-hydroxytryptamine, 5-HT)2A receptors causes impulsivity and attentional deficits. Since 5-HT2A are known to entertain antagonistic interactions with metabotropic glutamate (mGlu)2/3 receptors, this interaction may provide an alternative target for a novel class antipsychotics. The study characterizes between mGlu2/3 implicated in impulse control. Hooded Lister rats were trained 5-choice serial reaction time task (5-CSRTT) treated the 5-HT2A/2C receptor agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride (DOI, 0.1 mg/kg) LY379268 (1 mg/kg). In addition, associated drug-induced changes neuronal activity assessed via c-Fos immunoreactivity (Fos IR), co-localization GABAergic markers was detected using double immunofluorescence labeling. Systemic DOI caused impulsive overresponding that attenuated animals pre-treated LY379268. itself had no significant effect on rats' performance 5-CSRTT. enhanced Fos IR within fronto-cortical limbic brain structures, blocked by pre-treatment. Double labeling showed specific DOI-elicited (GAD67-positive) cells lacking calcium-binding protein parvalbumin while increased non-GABAergic cells. Our results suggest is possibly due primary increase Glu transmission mediated activation. Thus, agonists might have some potential treating motor impulsivity-related impairments their cognitive enhancing effects not confirmed study.