Emotional and risk seeking behavior after prepuberal subchronic or adult acute stimulation of 5-HT7-Rs in Naples High Excitability rats

Synapse. 2014 Apr;68(4):159-67. doi: 10.1002/syn.21724. Epub 2013 Dec 2.


We report here the results of studies aimed to investigate the involvement of serotonin receptor 7 subtype (5-HT7-R) in the modulation of emotional response in Naples High-Excitability (NHE) rat, a validated model for hyperactivity and impaired attention. A range of dosages (0.0, 0.125, 0.250, or 0.500 mg/kg) of LP-211, a selective agonist of 5-HT7-Rs, has been evaluated in animals at different age (adolescence and adulthood). Male NHE and random bred (NRB) control rats were tested in an Elevated Zero-Maze (EZM) after LP-211 treatment in two different regimens: at the issue of adolescent, subchronic exposure (14 intraperitoneal [i.p.] injections, once/day, pnd 31-44, tested on pnd 45--Exp. 1) or as adult, acute effect (15 min after i.p. injection--Exp. 2). Adolescent, subchronic LP-211 at 0.500 mg/kg dosage increased the frequency of head-dips only in NHE rats. Drug effect on time spent and entries in open EZM quadrants were revealed with adult, acute administration of 0.125 mg/kg LP-211 (both strains), indicating a tendency toward anxiolytic effects. In conclusion, data demonstrate that subchronic stimulation of 5-HT7-Rs during prepuberal period increases novelty-seeking/risk-taking propensity in NHE adults. These sequels are revealing increased disinhibition and/or motivation to explore in the NHE rats, which are characterized by a hyperactive dopaminergic system. These data may open new perspectives in studying mechanism of risk-seeking behavior.

Keywords: ADHD; LP-211; NHE rats; hyperactivity; zero maze.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Attention / drug effects
  • Emotions / drug effects*
  • Male
  • Piperazines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / metabolism*
  • Risk-Taking*
  • Serotonin Receptor Agonists / pharmacology*


  • N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide
  • Piperazines
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • serotonin 7 receptor