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 affec t the neuroendocrine response to a novel environment and other stresso rs. Introduction to a novel environment also increases neurotransmitte r turnover in the medial prefrontal cortex (MPFC). In this study, we e xamined the possibility that gonadal steroid hormones could similarly modulate the neurotransmitter response to a novel environment in the M PFC of the male rat. Male Fischer 344 rats at 3 months of age were gon adectomized (GDX'd) and implanted with Silastic capsules containing di hydrotestosterone propionate (DHTP, a non-aromatizable form of androge n), 17 beta-estradiol (E), or placebo. Control animals were left intac t. 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 fr om their home cage. Using high performance liquid chromatography, the MPFC was assayed for tissue levels of dopamine (DA) and its metabolite s, 3,4-dihydroxyphenylalanine (DOPAC) and homovanillic acid (HVA); nor epinephrine (NE) and its metabolite 3-methoxy-4-hydroxyphenylglycol (M HPG); or serotonin (5-HT) and its metabolite 5-hydroxyindole acetic ac id (5-HIAA). The introduction to a novel environment caused significan t increases in turnover of all three neurochemicals examined as estima ted by metabolite/precursor ratios. These increases were characterized by increases in DOPAC, HVA, MKPG and 5-HIAA coupled with decreases in DA, NE and 5-HT. There was no effect of GDX on neurotransmitter turno ver, however, treatment of GDX animals with DHTP prevented the open fi eld induced increase in DOPAC/DA, MHPG/NE, and 5-HIAA/5-HT ratio. Trea tment of GDX animals with estrogen had the opposite effect of DHTP, DO PAC/DA and MHPG/NE ratios increased to a greater level following the i ntroduction to a novel environment than in GDX or intact animals. Exam ination of behavior in the open field showed significant decreases in activity in the DHTP-treated group but not in any other behavioral par ameter Gears, nose pokes). Since the non-aromatizable androgen, DHTP, is presumably acting via androgen receptors, and E is presumably actin g via estrogen receptors, these data suggest that, in the MPFC of male rats, androgen and estrogen receptors act in an opposing fashion to m odify neurotransmitter turnover. This suggests that local changes in t he relative levels of androgen and estrogen can have profound effects on the neurobiological response of the medial prefrontal cortex to sti muli. (C) 1997 Elsevier Science B.V.