The cross-talk at the prefronto-striatal interface involves excitatory amino acids, different receptors and transducers as well as various modulators such as dopamine, serotonin (5-HT), norepinephrine, histamine. The aim of these studies was to investigate long-term effects of prepuberal subchronic 5HT7 receptor stimulation in adulthood. Male Naples High-Excitability (NHE) rats, and their Random-Bred (NRB) controls received prepuberal (pnd 28-42) subchronic 5HT7 receptor agonist LP211 (0.0, 0.125, 0.250 or 0.500 mg/kg, i.p., daily) administration. Rats were tested as young adults (pnd 70-75) in Làt- and Olton-mazes, for activity, non selective and selective spatial attention (SSA). In NHE rats, LP211 0.125 mg/kg reduced horizontal activity, whereas 0.250 mg/kg increased SSA in the Olton-maze. L-Glutamate and L-Aspartate were evaluated in prefrontal cortex (PFC), dorsal (DS) and ventral striatum (VS). Liquid Chromatography Coupled to Tandem Mass Spectrometry (LC-MS-MS) on supernatants from ice-cold saline homogenates centrifuged at 13,000g at 4°C per 20 min demonstrated that LP211 decreased L-Glu and L-Asp in DS after 0.125 mg/kg and increased L-Glu in PFC and L-ASP in VS after 0.250 mg/kg in NHE rats. L-Glu was persistently decreased after 0.125 mg/kg only in VS of NRB rats. Thus, prepuberal serotonergic stimulation permanently modifies neural circuits underlying activity motivation and attention at the prefronto-striatal interface of an animal model of hyperactivity and attention deficit.

(This research was supported by an Young-Investigator Project, to LAR by Italian Ministry of Health).