Behavioural phenotyping of male growth hormone-releasing hormone (GHRH) knockout mice

Abstract

ObjectiveGH-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). DesignHomozygous 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. ResultsGHRHKO 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). ConclusionThese 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.