Androgen inhibits neurotransmitter turnover in the medial prefrontal cortex of the rat following exposure to a novel environment.
Previous studies have demonstrated that gonadal steroid hormones affect the neuroendocrine response to a novel environment and other stressors. Introduction to a novel environment also increases neurotransmitter turnover in the medial prefrontal cortex (MPFC). In this study, we examined the possibility that gonadal steroid hormones could similarly modulate the neurotransmitter response to a novel environment in the MPFC of the male rat. Male Fischer 344 rats at 3 months of age were gonadectomized (GDX'd) and implanted with Silastic capsules containing dihydrotestosterone propionate (DHTP, a non-aromatizable form of androgen), 17 beta-estradiol (E), or placebo. Control animals were left intact. Each of these groups was further divided into a group introduced to a novel environment or a home cage control group. Animals exposed to a novel environment were killed after spending 20 min in a novel open field, whereas control animals were killed immediately upon removal from their home cage. Using high performance liquid chromatography, the MPFC was assayed for tissue levels of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylalanine (DOPAC) and homovanillic acid (HVA); norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG); or serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA). The introduction to a novel environment caused significant increases in turnover of all three neurochemicals examined as estimated by metabolite/precursor ratios. These increases were characterized by increases in DOPAC, HVA, MHPG and 5-HIAA coupled with decreases in DA, NE and 5-HT. There was no effect of GDX on neurotransmitter turnover, however, treatment of GDX animals with DHTP prevented the open field induced increase in DOPAC/DA, MHPG/NE, and 5-HIAA/5-HT ratio. Treatment of GDX animals with estrogen had the opposite effect of DHTP, DOPAC/DA and MHPG/NE ratios increased to a greater level following the introduction to a novel environment than in GDX or intact animals. Examination of behavior in the open field showed significant decreases in activity in the DHTP-treated group but not in any other behavioral parameter (rears, nose pokes). Since the non-aromatizable androgen, DHTP, is presumably acting via androgen receptors, and E is presumably acting via estrogen receptors, these data suggest that, in the MPFC of male rats, androgen and estrogen receptors act in an opposing fashion to modify neurotransmitter turnover. This suggests that local changes in the relative levels of androgen and estrogen can have profound effects on the neurobiological response of the medial prefrontal cortex to stimuli.
Handa
R J
RJ
Department of Cell Biology, Loyola University, Chicago, Stritch School of Medicine, Maywood, IL 60153, USA. rhanda@wpo.it.luc.edu
Hejna
G M
GM
Lorens
S A
SA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000378:metabolism
D018377:Neurotransmitter Agents; D013196:Dihydrotestosterone; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D004295:Dihydroxyphenylalanine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid