title: Behavioural phenotyping of male growth hormone-releasing hormone (GHRH) knockout mice.
abstract: OBJECTIVE
  GH-releasing hormone (GHRH) is a key regulator of GH secretion. The role of GH in anxiety is somewhat contradictory. The aim of this study is to elucidate the consequences of lack of GHRH on emotional behaviour in a mouse model of GH deficiency due to removal of the GHRH gene (GHRH knock out, GHRHKO).
  
  
  METHODS
  Homozygous GHRHKO and wild type male mice were utilized for this study. The emotional behaviour was measured through a battery of behavioural tests (locomotor activity/open field, light-dark exploration, elevated plus maze, forced swim test, tail suspension test). To correlate the emotional behaviour with brain neurochemistry, we evaluated thyrotropin-releasing hormone (TRH) gene expression in hypothalamic tissue by real-time PCR, and the levels of norepinephrine (NE), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) in prefrontal cortex by HPLC analysis.
  
  
  RESULTS
  GHRHKO mice showed increased exploratory activity. In the open field test (P<0.005), light-dark box (P<0.005) and elevated plus maze (P<0.05), GHRHKO mice demonstrated a decrease in anxiety-related behaviour. In addition, GHRHKO mice showed reduced immobility time with respect to control in forced swim test and tail suspension test (P<0.0001). The gene expression of hypothalamic TRH (P<0.05) was increased, while NE levels in prefrontal cortex were decreased compared to control (P<0.05).
  
  
  CONCLUSIONS
  These results suggest that in male mice GHRH deficiency brings about an increased physical activity and decreased anxiety- and depression-related behaviour, possibly related to increased TRH and decreased NE levels in the brain.
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Sheila
authors.initials: S
authors.lastname: Leone
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Rugia
authors.initials: R
authors.lastname: Shohreh
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Manippa
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Recinella
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ferrante
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Giustino
authors.initials: G
authors.lastname: Orlando
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvatori
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Vacca
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy. Electronic address: brunetti@unich.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Brunetti
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology; D000818:Animals; D001007:Anxiety / Q000235:genetics; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics*; D008297:Male; D018782:Maze Learning; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009638:Norepinephrine / Q000378:metabolism; D010641:Phenotype; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism
chemical_list: D013973:Thyrotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone; D009638:Norepinephrine
keywords: Anxiety; Depression; Growth hormone-releasing hormone knockout; Norepinephrine; Thyrotropin-releasing hormone