Impulsivity and home-cage activity are decreased by lentivirus-mediated silencing of serotonin transporter in the rat hippocampus

Abstract

Brain serotonin (5-HT) systems modulate emotional, motivational and cognitive processes. Mutations in the serotonin transporter (SERT) gene have been associated with susceptibility towards the development of several psychiatric disorders, both in humans and animal models. Present approach exploited a bilateral intra-hippocampus stereotaxic inoculation of lentiviruses, for enduring in vivo silencing of SERT. Control rats were bilaterally inoculated with heat-inactivated lentiviruses. These Lenti-SERT vectors were intended to eventually manipulate the neurotransmitter reuptake at synaptic level, thus enhancing tonic 5-HT transmission. We investigated whether such manipulation could induce behavioural alterations relevant to the modelling of ADHD, in particular symptoms of hyperactivity and impulsivity. Wistar rats were monitored for spontaneous home-cage locomotor activity and studied for impulsivity (Intolerance-to-Delay task). Results show that rats inoculated with Lenti-SERT vectors exhibited less pronounced circadian peaks of activity than controls. Moreover, Lenti-SERT compared to control rats exhibited a transient increase in choice for a delayed-larger reward over an immediate-small reward. This suggests that enhanced hippocampal serotonergic transmission produced a profile of restfulness and a decrease in cognitive impulsivity. This phenotype is consistent with available data both on 5-HT manipulations and hippocampal lesions. In conclusion, present findings may possibly disclose novel avenues towards the development of innovative therapeutical approaches for behavioural symptoms relevant to ADHD.