PMID- 24923983
OWN - NLM
STAT- MEDLINE
DCOM- 20151016
LR  - 20211021
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 232
IP  - 1
DP  - 2015 Jan
TI  - Persistent modification of forebrain networks and metabolism in rats following 
      adolescent exposure to a 5-HT7 receptor agonist.
PG  - 75-89
LID - 10.1007/s00213-014-3639-6 [doi]
AB  - RATIONALE: 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. OBJECTIVES: 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 perpendicular) 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.
FAU - Canese, Rossella
AU  - Canese R
AD  - Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, viale 
      Regina Elena 299, Rome, 00161, Italy, rossella.canese@iss.it.
FAU - Zoratto, Francesca
AU  - Zoratto F
FAU - Altabella, Luisa
AU  - Altabella L
FAU - Porcari, Paola
AU  - Porcari P
FAU - Mercurio, Laura
AU  - Mercurio L
FAU - de Pasquale, Francesco
AU  - de Pasquale F
FAU - Butti, Erica
AU  - Butti E
FAU - Martino, Gianvito
AU  - Martino G
FAU - Lacivita, Enza
AU  - Lacivita E
FAU - Leopoldo, Marcello
AU  - Leopoldo M
FAU - Laviola, Giovanni
AU  - Laviola G
FAU - Adriani, Walter
AU  - Adriani W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140613
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide)
RN  - 0 (Piperazines)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 0 (serotonin 7 receptor)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Magnetic Resonance Imaging/methods
MH  - Male
MH  - Nerve Net/drug effects/*metabolism
MH  - Piperazines/*pharmacology
MH  - Prosencephalon/drug effects/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Serotonin/*metabolism
MH  - Serotonin Receptor Agonists/*pharmacology
EDAT- 2014/06/14 06:00
MHDA- 2015/10/17 06:00
CRDT- 2014/06/14 06:00
PHST- 2013/10/28 00:00 [received]
PHST- 2014/05/22 00:00 [accepted]
PHST- 2014/06/14 06:00 [entrez]
PHST- 2014/06/14 06:00 [pubmed]
PHST- 2015/10/17 06:00 [medline]
AID - 10.1007/s00213-014-3639-6 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2015 Jan;232(1):75-89. doi: 10.1007/s00213-014-3639-6. 
      Epub 2014 Jun 13.