Modulatory effects following subchronic stimulation of brain 5-HT7-R system in mice and rats

Rev Neurosci. 2014;25(3):383-400. doi: 10.1515/revneuro-2014-0007.


The serotonin receptor 7 (5-HT7-R) plays important functional roles in learning and memory, in regulation of mood and circadian rhythmicity. LP-211 is a new selective agonist, belonging to 1-arylpiperazine category. We report studies aimed to evaluate the modulatory effect of a subchronic regimen on behavioral/molecular parameters. At low dose [0.25 mg/kg intraperitoneally (i.p.)], LP-211 induced a 6-h anticipated wake up in adult mice (with no temporal landmark by constant light), acting as nonphotic stimulus for 'internal clock' resetting. In standard 12:12-h light/dark cycle, a subchronic effect (5-6 days at 0.25 mg/kg, once per day) was observed: delayed wake up, reduced peak of locomotor activity and no evidence for brain cellular proliferation after ex vivo analysis. Other studies in rats were aimed to investigate long-term effects of developmental LP-211 administration into adulthood. Subchronic LP-211 (0.125 mg/kg i.p. once per day during the prepuberal phase) reduced l-glutamate, N-methyl-d-aspartate receptor 1 and dopamine transporter within the ventral striatum. With LP-211 (0.25 mg/kg i.p. once per day during the postpuberal phase), clear reductions were observed in the immunoreactivity of serotonin transporter and dopaminergic D2 receptors in the ventral and dorsal striatum, respectively. Subchronic LP-211 in rats and mice appears to be a suitable tool for studying the role of 5-HT7-R in sleep disorders, emotional/motivational regulations, attentive processes and executive functions.

Publication types

  • Review

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Brain / drug effects
  • Brain / metabolism*
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology*
  • Mice
  • Piperazines / pharmacology
  • Rats
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Serotonin Receptor Agonists / pharmacology
  • Time Factors


  • N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide
  • Piperazines
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Receptor Agonists
  • serotonin 7 receptor