title: Persistent modification of forebrain networks and metabolism in rats following adolescent exposure to a 5-HT7 receptor agonist.
abstract: BACKGROUND
  The serotonin 7 receptor (5-HT7-R) is part of a neuro-transmission system with a proposed role in neural plasticity and in mood, cognitive or sleep regulation.
  
  
  OBJECTIVE
  We investigated long-term consequences of sub-chronic treatment, during adolescence (43-45 to 47-49 days old) in rats, with a novel 5-HT7-R agonist (LP-211, 0 or 0.250 mg/kg/day).
  
  
  METHODS
  We evaluated behavioural changes as well as forebrain structural/functional modifications by in vivo magnetic resonance (MR) in a 4.7 T system, followed by ex vivo histology.
  
  
  RESULTS
  Adult rats pre-treated during adolescence showed reduced anxiety-related behaviour, in terms of reduced avoidance in the light/dark test and a less fragmented pattern of exploration in the novel object recognition test. Diffusion tensor imaging (DTI) revealed decreased mean diffusivity (MD) in the amygdala, increased fractional anisotropy (FA) in the hippocampus (Hip) and reduced axial (D||) together with increased radial (D⊥) diffusivity in the nucleus accumbens (NAcc). An increased neural dendritic arborization was confirmed in the NAcc by ex vivo histology. Seed-based functional MR imaging (fMRI) identified increased strength of connectivity within and between "limbic" and "cortical" loops, with affected cross-correlations between amygdala, NAcc and Hip. The latter displayed enhanced connections through the dorsal striatum (dStr) to dorso-lateral prefrontal cortex (dl-PFC) and cerebellum. Functional connection also increased between amygdala and limbic elements such as NAcc, orbito-frontal cortex (OFC) and hypothalamus. MR spectroscopy (1H-MRS) indicated that adolescent LP-211 exposure increased glutamate and total creatine in the adult Hip.
  
  
  CONCLUSIONS
  Persistent MR-detectable modifications indicate a rearrangement within forebrain networks, accounting for long-lasting behavioural changes as a function of developmental 5-HT7-R stimulation.
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, viale Regina Elena 299, Rome, 00161, Italy, rossella.canese@iss.it.
authors.forename: Rossella
authors.initials: R
authors.lastname: Canese
authors.forename: Francesca
authors.initials: F
authors.lastname: Zoratto
authors.forename: Luisa
authors.initials: L
authors.lastname: Altabella
authors.forename: Paola
authors.initials: P
authors.lastname: Porcari
authors.forename: Laura
authors.initials: L
authors.lastname: Mercurio
authors.forename: Francesco
authors.initials: F
authors.lastname: de Pasquale
authors.forename: Erica
authors.initials: E
authors.lastname: Butti
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
authors.forename: Enza
authors.initials: E
authors.lastname: Lacivita
authors.forename: Marcello
authors.initials: M
authors.lastname: Leopoldo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Laviola
authors.forename: Walter
authors.initials: W
authors.lastname: Adriani
mesh_terms: D000367:Age Factors; D000818:Animals; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: C573815:N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide; D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor