MODULATORY EFFECTS FOLLOWING SUBCHRONIC STIMULATION OF BRAIN 5-HT7 RECEPTOR SYSTEM IN MICE AND RATS

The serotonin receptor 7 (5-HT7-R), is very abundant in the thalamus, hypothalamus, dorsal raphe nucleus and hippocampus; at lower levels it is found also in the cortex, striatum and amygdala. This neurochemical receptor system plays important functional roles in learning and memory, in regulation of mood and circadian rhythmicity. Recently, many agonist drugs selective for this receptor have been developed and their effects reported. Presently, we review some recent studies we have conducted aimed to evaluate the modulatory effect of a subchronic regimen with LP-211, a new selective agonist compound belonging to 1-arylpiperazine category, on behavioural and molecular parameters. At low dose (0.25 mg/kg, i.p.), LP-211 induced in adult mice a six-hour anticipated wake up with no temporal landmark (constant light) acting as non-photic stimulus for “internal clock” resetting. In standard 12:12h L/D cycle, we observed a subchronic effect (5-6 days at 0.25 mg/kg, once/day), on delay of wake up associated with a reduction of peak locomotor activity and any evidence for a real cellular proliferation after ex vivo analysis. The other studies, conduct on rats, were aimed to investigate long-term effects of subchronic LP-211 administration into adulthood development. Subchronic LP-211 (0.125 mg/kg, i.p. once/day) during the prepuberal phase reduced L-Glutamate, NMDAR1 and DAT, within the ventral striatum. Moreover, we observed a clear reduction of the immunoreactivity of serotonin transporter (SERT) and dopaminergic D2 receptors at dorsal striatum. These results represent a starting point to explore the neurophysiology of 5-HT7-R: subchronic LP-211 in rats and mice appears a suitable tool for studying the role of 5-HT7-R in sleep disorders, emotional and motivational regulations, attentive processes and executive functions.