INHIBITION OF GH IN MATERNAL SEPARATION MAY BE MEDIATED THROUGH ALTERED SEROTONERGIC ACTIVITY AT 5-HT2A AND 5-HT2C RECEPTORS

The hyposecretion of growth hormone (GH) in maternal separation (MS) o f rat pups is remarkably similar to the specific suppression of GH sec retion to evocative tests in infants diagnosed with Reactive Attachmen t Disorder of Infancy (RADI). Growth hormone-releasing factor (GRF) an d somatostatin (SS) provide opposing regulation of GH secretion, and b oth are modified by noradrenergic and serotonergic stimuli in neonatal and adult rats. In this study, GRF administration reversed MS-induced suppression of GH secretion in 10-day-old pups, but this action of GR F was prevented by pretreatment with cyproheptadine (Cypro), a seroton ergic antagonist. The normalization of GH secretion after return to th e dam was not altered by pretreatment with SS. Indirect 5-HT agonists, fluoxetine (FLX) and 5-HTP, both stimulated GH secretion in 10-day-ol d pups. All mixed serotonin- and 5-HT1A-receptor agonists suppressed G H secretion in 10-day-old pups. Antagonists Cypro and ketanserin (Ket) suppressed FLX-induced GH secretion. In contrast, only Cypro suppress ed 5-HTP-induced GH secretion. Maternal separation inhibited GH secret ion stimulated by 5-HTP, but not by FLX. The serotonergic pathway acti ng on 5-HT2A receptors may be obligatory for GRF-mediated stimulation and is sensitive to inhibition by Cypro. In addition, a Ket-sensitive serotonergic parallel pathway acting on 5-HT2C receptors may also stim ulate GH secretion by acting on GRF or SS. However, only the obligate 5-HT2A pathway appears to be suppressed in MS. These data and observat ions by others indicate that specific suppression of GH secretion in M S may derive from a reduction in GRF release through noradrenergic neu rons, possibly impinging upon serotonergic terminals in the hypothalam us. This study may also provide insight into mechanisms by which GH se cretion is suppressed in humans with RADI. Copyright (C) 1996 Elsevier Science Ltd