Gail D. Riegle

Chronic stress effects on adrenocortical responsiveness in young and aged rats.

The effect of chronic stress on adrenocorticalfunction was tested in young and aged male and female rats. The rats were subjected twice a day to 2 h restraint stress for 20 days. Adrenocortical responsiveness to stressors was decreased during the treatment in all groups. Responsiveness to ACTH injection was greater than stress responsiveness in all groups. The decrease in stress responsiveness was greater in the young than in the aged groups. The data suggest that elevated corticosterone concentrations from chronic stress adrenocortical activation result in incomplete feedback inhibition of the adrenocortical control mechanism. The increased inhibition in the young groups supports the concept of decreased adrenocortical control system sensitivity in the aged animal.

Characteristics of dopaminergic neurons in the aged male rat.

Male rats were sacrificed at 5 months (young rats) or at 24 months (aged rats). When compared with values in young rats, aged rats had higher serum concentrations of prolactin and lower concentrations of luteinizing hormone and testosterone. In the median eminence, which contains the terminals of tuberoinfundibular dopamine (DA) neurons, the concentrations of DA and dihydroxyphenylactic acid (DOPAC), and the rate of DA synthesis (accumulation of DOPA after the inhibition of DOPA decarboxylase) were decreased in aged rats. In the striatum, which contains the terminals of nigrostriatal DA neurons, the concentration of DA was reduced, but this change was not accompanied by a decrease in DOPAC concentrations or DOPA accumulation. The decreased DA concentration observed in the median eminence and striatum of aged rats may reflect the loss of DA neurons. An attempt was made to mimic the age-related loss of nigrostriatal and tuberoinfundibular DA neurons by pretreating rats with intraventricular injections of 6-hydroxydopamine. In these animals the decrease of DA in the median eminence was accompanied by a concomitant reduction in the rate of DOPA accumulation, whereas in the striatum the concentration of DA was reduced, but DOPA accumulation remained normal. These results suggest that in aged and 6-hydroxydopamine-treated rats, the loss of nigrostriatal DA neurons is accommodated for by a compensatory increase in the activity of the remaining neurons whereas tuberoinfundibular DA neurons are unable to compensate in a similar manner.

Biochemical indices of tuberoinfundibular dopaminergic neuronal activity during lactation: A lack of response to prolactin

Serum concentrations of prolactin and biochemical estimates of impulse traffic in dopaminergic neurons (neuronal ‘activity’) were compared in rats on the second day of diestrus and in 12-day postpartu

Sexual Differences in Tuberoinfundibular Dopamine Nerve Activity Induced by Neonatal Androgen Exposure

The activities of different catecholaminergic neurons in the brains of male amd female rats were estimated by measuring (1) the rate of decline of dopamine (DA) and norepinephrine (NE) after inhibition of tyrosine hydroxylase with alpha-methyltyrosine (alpha-MT) and (2) the rate of accumulation of dihydroxyphenylalanine (DOPA) after inhibition of DOPA decarboxylase with NSD 1015 in brain regions containing the terminals of these neurons. In the median eminence the accumulation of DOPA and the alpha-MT-induced decline of DA, but not NE, were higher in the female than in the male, suggesting increased activity of tuberoinfundibular DA neurons in the female. There were no sexual differences in DA neurons which terminate in any of the other brain regions (striatum, olfactory tubercle, nucleus accumbens, posterior pituitary). To determine if the sexual difference in tuberoinfundibular DA neuronal activity results from neonatal exposure to androgens, the rate of DOPA accumulation was examined in the median eminence of females, males, and androgen-sterilized females (all of which were castrated as adults) and in adult males which were castrated as neonates. Similar values for DOPA accumulation were observed in the median eminence of castrate females and neonatally castrated males, while significantly lower values were observed in castrate males and androgen-sterilized females. Thus, neonatal exposure to androgens alters the activity of tuberoinfundibular DA neurons. Neonatal androgen-induced differences in tuberoinfundibular DA neuronal activity may be responsible, in part, for sexual differences in the hypothalamic regulation of hypophyseal hormone secretion.

Chronic and acute dexamethasone suppression of stress activation of the adrenal cortex in young and aged rats.

Adrenocortical responsiveness to ether vapor stress was measured in young adult (4–6 months) and aged (22–32 months) rats subjected to acute and chronic treatments with dexamethasone. Daily administra

Dopaminergic neuronal function, anterior pituitary dopamine content, and serum concentrations of prolactin, luteinizing hormone and progesterone in the aged female rat

The serum concentrations of prolactin (PRL), progesterone and luteinizing hormone (LH), and the content and rate of synthesis of dopamine (DA) in selected brain regions were determined in young (3-6 months), intermediate (13-15 months) and aged (24-25 months) female Long-Evans rats. Young rats were examined on the days of diestrus 2 and estrus. Intermediate rats were divided into 2 groups, a group which was cycling regularly (examined on the day of estrus) and a group which exhibited constant estrus. Aged rats were divided into 3 groups one which cycled regularly (examined on day of estrus), one which exhibited constant estrus, and one which exhibited repetitive pseudopregnancies. Serum PRL was increased in all intermediate and aged rats when compared to values in young animals. Serum LH was increased and progesterone decreased in those intermediate and aged rats which exhibited constant estrous reproductive patterns. The DA content was generally decreased in the median eminence, posterior pituitary, striatum, nucleus accumbens and olfactory tubercle of all aged rats, while the rate of DA synthesis was decreased only in the median eminence of aged, non-cycling rats. This suggests that all DA neuronal systems except those in the tuberoinfundibular system are able to compensate for the age-related loss. Despite the apparent reduction of tuberoinfundibular DA neuronal function the concentration of DA in the anterior pituitary, which is believed to represent amine released from the neurons, is dramatically increased in intermediate age rats in constant estrus, and in all groups of aged rats. The maintenance of high PRL secretion despite the elevated content of DNA in the anterior pituitary suggests an age-related defect in the dynamics of DA in this gland; this defect may contribute to the loss of reproductive function in the aging rat.

Long-Term Treatment with Estradiol Induces Reversible Alterations in Tuberoinfundibular Dopaminergic Neurons: a Decreased Responsiveness to Prolactin

Previous studies have demonstrated that short-term (3-5 days) treatment with estradiol increases the rate of turnover and synthesis of dopamine (DA) in terminals of tuberoinfundibular (TI) neurons in the median eminence by virtue of the ability of this hormone to increase circulating concentrations of prolactin. The present studies were undertaken to examine the long-term effects of estradiol on serum prolactin concentrations and TIDA neuronal activity (estimated by the rate of DOPA accumulation in the median eminence after the administration of a decarboxylase inhibitor). Female rats, ovariectomized for 2 weeks, were implanted subcutaneously with silastic capsules containing estradiol benzoate and sacrificed 6, 12 and 18 days after capsule implantation. Serum prolactin concentrations were markedly increased at 6, 12 and 18 days whereas the rate of DOPA accumulation was increased at 6 days but not at 12 days, and was decreased at 18 days. The concentration of DA in the median eminence was reduced at 6 days and further reduced at 12 and 18 days. The low rate of DOPA accumulation in the median eminence despite the high circulating concentrations of prolactin suggests that long-term estradiol treatment reduces the ability of TIDA neurons to respond to prolactin. This was confirmed by the finding that direct intracerebroventricular (icv) injections of prolactin increased the rate of DOPA accumulation in the median eminence of sham-implanted rats but not in 18 day estradiol-treated rats. To determine if the effects of estradiol were reversible, ovariectomized rats were implanted with estradiol-containing capsules for 18 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Aging on LH and Prolactin after LHRH L-Dopa, Methyl-Dopa, and Stress in Male Rat

Summary Hypothalamic-pituitary control of prolactin and LH secretion was tested in young (4-6 months) and aged (22-30 months) male Long-Evans rats given l-dopa, methyl dopa, LHRH, or stress treatments. Pretreatment serum LH levels were consistently higher in young than in the aged groups. The increase in serum LH after LHRH injection was only about half as much in aged as compared to young control males. Although acute stress caused a prompt increase in serum LH in young male rats, this treatment was without effect in the aged group. Methyl dopa treatment stimulated serum prolactin secretion in both young and old rats. Although L-dopa treatment caused a reduction in serum prolactin in both age groups, the sensitivity, magnitude, and duration of the reduction was smaller in the aged rats.

Acute Restraint Stress Decreases Dopamine Synthesis and Turnover in the Median Eminence: A Model for the Study of the Inhibitory Neuronal Influences on Tuberoinfundibular Dopaminergic Neurons

The effects of acute stress on serum prolactin concentrations and tuberoinfundibular dopaminergic (TIDA) neuronal activity were studied in female rats. TIDA neuronal activity was estimated by measuring the rate of dihydroxyphenylalanine (DOPA) accumulation after the administration of a decarboxylase inhibitor (NSD 1015) and the rate of decline of dopamine (DA) after the administration of a tyrosine hydroxylase inhibitor (alpha-methyltyrosine) in the median eminence. Serum prolactin concentrations were increased following 30 min of supine immobilization (restraint stress), but returned to control levels by 2, 8, and 16 h after the onset of this stress. The rate of DOPA accumulation was decreased during the 30 min of restraint; it was still further reduced 2 h later but had returned to control levels 8 and 16 h later. No change in the rate of DOPA accumulation was observed in the striatum or neurointermediate lobe of the pituitary at any time after the start of restraint. Restraint stress also decreased the rate of DA turnover in the median eminence, but was without effect on the rates of DA turnover in the striatum or neurointermediate lobe. These results suggest that restraint stress activates an inhibitory neuronal pathway which decreases the activity of TIDA neurons and may be responsible, at least in part, for the increase in serum prolactin concentrations. The responsiveness of TIDA neurons to the stress-induced decrease in activity was not influenced by the time of day or the stage of the estrous cycle. Not all stressful manipulations decreased TIDA neuronal activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging effects on hypothalamic dopamine and norepinephrine content in the male rat.

Hypothalamic content of dopamine and norepinephrine was measured in young (4 mo) and aged (24-26 mo) male rats by aluminum oxide adsorption and microfluorescence. Hypothalamic content of both dopamine and norepinephrine was significantly less in aged than in the young groups. Average dopamine content of the young and aged groups was 32.5 +/- 9.3 and 15.6 +/- 2.5 ng/hypothalamus, respectively. Norepinephrine content averaged 47.6 +/- 10.7 and 22.8 +/- 1.8 ng/hypothalamus in the young and aged groups. These data suggested that alterations in hypothalamic catecholamine function contribute to changes in endocrine control mechanisms during aging.