Haloperidol ameliorates androgen-induced behavioral deficits in developing male rats

Abstract

The purpose of present study was to infer the potential effects of testosterone increase in some male-based childhood-onset neuropsychiatric disorders, such as Tourette syndrome. Thus, the influence of early postnatal androgen exposure upon the neurobehaviors and its possible neural basis were investigated in the study. Male pup rats received consecutive 14-day testosterone propionate (TP) subcutaneous injection from postnatal day (PND) 7. The TP treatment produced the hyperactive motor behavior and grooming behavior as well as the increased levels of dopamine, tyrosine hydroxylase and dopamine transporter in the mesodopaminergic system and the elevated levels of serotonin in the nucleus accumbens, without affecting the levels of glutamate, γ-aminobutyric acid, norepinephrine and histamine in the caudate putamen and nucleus accumbens of PND21 and PND49 rats. Dopamine D2 receptor antagonist haloperidol was administered to the early postnatal TP-exposed PND21 and PND49 male rats 30 min prior to open field test. Haloperidol significantly ameliorated the motor behavioral and grooming behavioral defects induced by early postnatal TP exposure. The results demonstrated that early postnatal androgen exposure significantly disturbed the brain activity of developing male rats via enhancing the mesodopaminergic activity. It was suggested that abnormal increments of testosterone levels during the early postnatal development might be a potential risk factor for the incidence of some male-based childhood-onset neuropsychiatric disorders by affecting the mesodopaminergic system.

Effects of Acupuncture on Behavioral Stereotypies and Brain Dopamine System in Mice as a Model of Tourette Syndrome

“…Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis in the brain and is responsible for the conversion of L -tyrosine to 3,4 dihydrophenylalanine (DOPA) (Brett et al, 1995; Zhu et al, 2012; Tekin et al, 2014). Dysregulation of TH activity is essential in the pathogenesis of TS (Brett et al, 1995; Comings et al, 1995; Qi et al, 2018).…”

Restricted effects of androgens on glucocorticoid signaling in the mouse prefrontal cortex and midbrain

“…Activated AR can increase Th promoter activity in cell lines ( 49 ). In several studies in adolescent male rats androgens where shown to stimulate TH and S lc6a3 mRNA or protein expression ( 50 – 53 ). The discrepancies between these observations and the results obtained by us and others could be influenced by either the age of the animals or possibly by a species difference between mice and rats.…”

Opinion on the impact of non‐monotonic dose responses on EFSA′s human health risk assessments

“…There is information indicating that postnatal increases in testosterone levels under certain conditions may trigger pathways resulting in adverse outcomes, although the relevance of these findings for experimental postnatal studies with phthalates is unclear. Examples cover experimental, human and epidemiological studies associating testosterone increase with neurological and neurodevelopmental effects (Qi et al., 2018; Nakano et al., 2010; Hines, 2003; Schwarz et al., 2011) and apical effects associated with overexpression of androgens (Hotchkiss et al., 2007; Martin et al., 1998). There are also some epidemiological studies linking phthalate exposure with metabolomic alterations (Zhou et al., 2018, neurodevelopmental Braun, 2017, Engel et al., 2018) and effects attributable to hyperandrogenism (Colon et al., 2000).…”

“…There is information indicating that postnatal increases in testosterone levels under certain conditions may trigger pathways resulting in adverse outcomes. Examples cover experimental, human and epidemiological studies associating testosterone increase with neurological and neurodevelopmental effects (Qi et al., 2018; Nakano et al., 2010; Hines, 2003; Schwarz et al., 2011). Other authors link testosterone stimulation with apical effects associated with overexpression of androgens (Hotchkiss et al., 2007; Martin et al., 1998).…”