Reduction In Dopamine Turnover Research Articles

Effects of estrogen on dopamine turnover, glutamic acid decarboxylase activity and lordosis behavior in septal lesioned female rats

Estradiol benzoate (EB) treatment (2.0 μg/day × 3) of septal lesioned adult female rats produces a marked increase in lordosis behavior over similarly treated sham operated animals. In these animals endogenous dopamine (DA) and norepinephrine (NE) levels were measured and turnover rates were estimated following tyrosine hydroxylase inhibition with α-methyltyrosine, in both EB and oil (0.05 ml × 3 days) treated groups. No consistent pattern of change in the level or rate of turnover of NE was noted for any of the treatment groups. No differences in either the level or turnover of DA were seen in the oil treated septal lesioned group, relative both to EB and oil treated sham operated groups. However, in the amygdala, corpus striatum and nucleus accumbens septi of the septal lesioned animals primed with EB there was both a reduction in endogenous levels (20–50%) and a decrease in synthesis rates (30–70%) of DA relative to both EB and oil treated sham operated groups and the oil treated septal lesioned group. The EB treated septal lesioned animals showed a significant negative correlation between DA levels in the corpus striatum and the level of lordosis behavior ( r = −.850), supporting the concept of a possible inhibitory role for DA on female sexual receptivity. Glutamic acid decarboxylase (GAD; the rate limiting enzyme in the synthesis of γ-aminobutyric acid (GABA)) activity was measured in the substantia nigra and ventral tegmental region from the same animals. GAD activity was reduced in both areas in the EB primed sham operated animals, while the EB and oil treated septal lesioned groups remained comparable to the oil treated sham operated animals. Because of the proposed existence of a GABA mediated inhibitory neuronal feedback on DA cell bodies in the midbrain, the reduction in DA turnover in the EB primed septal lesioned female rat and thus the increase in behavioral receptivity could be due in part to the failure of the septal lesioned animal to show a compensatory decrease in GAD activity.

Involvement of central catecholamines in the feedback actions of 17β-estradiolbenzoate on luteinizing hormone secretion in the ovariectomized female rat

(1) Evidence has been presented, based on quantitative microfluorimetric estimations of dopamine (DA) and noradrenaline (NA) levels and turnover, and on radioimmunological measurements of serum luteinizing hormone (LH), and follicle-stimulating hormone (FSH) and prolactin levels, that the central inhibitory feedback action of estradiol on LH secretion mainly involves a marked increase in DA turnover of the lateral palisade zone (LPZ) of the median eminence and also involves a reduction of NA turnover, mainly located in the medial preoptic area (MPOA) and in the subependymal layer (SEL). (2) The mechanism for these changes in catecholamine (CA) turnover is discussed. The possibility is favored that they involve the stimulation of central cytosol estrogen receptors which may even be located in the arcuate DA and possibly reticular NA cell bodies themselves. (3) The marked and long-lasting hypersecretion of prolactin caused by estrogen could be involved in mediating the sustained increase of DA turnover in the median eminence and the sustained reduction of NA turnover. (4) The central facilitatory feedback action of estrogen, on the other hand, may be mainly responsible for the sharp increase of NA turnover in the MPOA and SEL and also the associated reduction of DA turnover in the LPZ in the critical period of both adult cyclic rats and of immature female rats treated with PMS. (5) We take the view that these latter NA and DA turnover changes take precedence over cytosol estrogen receptors, which previous evidence indicates (see Sawyer, 1975) are located in preoptic and amygdaloid regions. (These estradiol concentrating neurons then directly and/or indirectly make connections with the NA and DA pathways). (6) FSH secretion is not controlled by DA and NA pathways. (7) The hypothesis given above is based on the assumption that different estradiol concentrating neurons are involved in the central inhibitory and facilitatory feedback action of estradiol and that the estrogen receptors of these respective neurons have differences which allow their differential activation, the inhibitory feedback leading mainly to a marked increase in the ratio DA activity/NA activity in the median eminence, whereas the facilitatory feedback causes a marked reduction of this ratio.