Age-related alteration in catecholamine activity within microdissected brain regions of ovariectomized fischer 344 rats

The effects of increasing age on catecholamine (CA) metabolism in microdissected brain regions and on serum and pituitary hormone levels were examined in ovariectomized Fischer 344 rats. Young (4 to 5 months old) and middle-aged (9 to 10 months old) normally cycling and old repeated pseudopregnant rats (21–22 months old, PP) were ovariectomized to eliminate the complicating effects of cyclic gonadal steroid fluctuations. CA metabolism was examined 2 weeks later. To determine CA turnover rates, each agegroup was subdivided into three groups, which were killed by decapitation 0, 45, or 90 min after administration of α-methyl-para-tyrosine (α-mpt). Dopamine (DA) and norepinephrine (NE) concentrations were determined in microdissected brain regions by radioenzymatic assay, and turnover rates were estimated. Steady-state concentrations of NE were not altered in middle-aged rats, but NE turnover rates increased in middle-aged rats in five of the six areas examined. While NE concentrations did not change with age in the median eminence (ME), NE turnover rates increased significantly in the two older age groups. These data indicate that the age-related decline in NE concentrations in several ventral diencephalic nuclei is preceded by a period of hyperactivity in noradrenergic neurons. DA concentrations were generally decreased in most areas examined in old versus young rats, with dramatic DA depletions (42–78%) observed in five regions. However, no consistent relationship between DA concentrations and turnover rates was seen either in regions with stable DA levels or in those which showed an age-associated decrease in DA concentrations. In the ME, a 42% decline in DA concentration was associated with an increase in the DA turnover rate in the oldest group of rats. Serum luteinizing hormone (LH) levels were similar in all three age groups of ovariectomized rats, while serum prolactin was elevated four-fold in old compared to younger animals. These data indicate that a complex pattern of regional alterations in CA metabolism accompanies the aging process and these may be related to the pseudopregnant state and hormone secretory capacity of aging Fischer 344 rats.     

Cyclic changes in the release of norepinephrine and dopamine in the medial basal hypothalamus: effects of aging

Push-pull perfusion and HPLC were used to measure the release of norepinephrine (NE) and dopamine (DA) in the medial basal hypothalamus of young (4–5 months old), middle-aged (8–10 months old), and old (22–24 months old) rats. In the young animals, the afternoon of proestrus was characterized by a gradual increase in NE release and a simultaneous gradual decrease in DA release. The peak in NE release and the nadir in DA release occurred at about the time when the proestrous surges in serum LH and PRL are known to occur. No changes in NE and DA releases occurred in the afternoon of diestrus when serum LH and PRL are known to remain stable. In the middle-aged proestrous animals, the patterns of NE and DA releases were similar to those in the young proestrous animals, but the peak in NE release was attenuated and did not reach statistical significance. This corresponded with the reported attenuation in the LH surge in middle age. In the old persistently diestrous animals, NE and DA were released at constant rates, which correlated with the well-documented constant levels of serum LH and PRL in old age. These data provide an explanation for the simultaneous proestrous surges of LH and PRL and lead us to conclude that NE plays a facilitatory role in the LH surge, while DA, through its inhibitory action, regulates the PRL surge. These studies, by monitoring NE and DA releases from adulthood through middle-age to old age, indicated that cyclicity in catecholamine (CA) activities begins to be dampened in middle-age and eventually completely disappears in the acyclic period of old age which is also characterized by a marked deficiency in CA activities.     

Effect of progesterone on monoamine turnover in the brain of the estrogen-primed rat

The effect of progesterone (P) on monoamine levels and turnover was evaluated in 8 brain nuclei in estrogen-primed rats. Animals were subcutaneously (SC) injected with P or vehicle 21 hours after SC treatment with 5 micrograms of estradiol benzoate (EB). EB-primed animals treated with P showed high levels of lordosis behavior and an LH surge three hours later. Initial concentrations of norepinephrine (NE), dopamine (DA), serotonin (5HT) and 5-hydroxyindole acetic acid were determined in EB-saline treated controls 3 hours after P or vehicle. NE and DA turnover was estimated from the exponential decline of these amines 2 hours after IP injection of alpha-methyl-p-tyrosine (5 hours after P or vehicle). The accumulation of 5HT 20 min following IP injection of pargyline was used as an index of 5HT turnover. P did not affect the initial NE, 5HT or 5HIAA concentrations in any of the brain nuclei studied, but decreased DA content in the arcuate-median eminence region (Ar-ME). The DA rate constant was elevated in the nucleus of the diagonal band of Broca and the DA turnover rate was decreased in the Ar-ME. In the periventricular region (PVE, anterior hypothalamic level) the NE turnover rate (K, pg/microgram protein/hr) and rate constant (k, hr-1) decreased following P treatment. Progesterone treatment decreased the accumulation of 5HT in the ventromedial hypothalamus (VMN, pars lateralis) and the dorsal midbrain central grey (MCG). Progesterone effects on monoamine turnover were not found in the lateral septal, medial preoptic, anterior hypothalamic or dorsal raphe nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreased Dopamine and Increased Norepinephrine Levels in the Spontaneously Epileptic Rat, a Double Mutant Rat

Summary: Dopamine (DA) and norepinephrine (NE) brain levels and turnover rate were examined in the spontaneously epileptic rat (SER: zi/zi, tm/tm), a double mutant rat obtained by mating tremor heterozygotes (tml +) with zitter homozygotes associated with epileptic seizures composed of spontaneously occurring tonic convulsion and absence-like seizure. DA and NE levels were also determined in age-matched male zitter, tremor and Kyo:Wistar rats. DA levels in caudate nucleus were significantly lower in adult age (10–12 weeks) SER, which showed epileptic seizures, and zitter rats than in adultKyo:Wistar and tremor rats. DA levels in other areas such as thalamus-hypothalamus, midbrain, and ponsmedulla were not different among SER, zitter, tremor, and Kyo:Wistar rats at age 10–12 weeks. Except in cerebral cortex and hippocampus, there were no differences in brain DA levels between young seizure-free SER (age 5 weeks) and young Kyo:Wistar rats. Furthermore, the turnover rate of DA was significantly lower in caudate nucleus of adult SER than of Kyo:Wistar rat, whereas in pons-medulla there was no difference between the two strains. In contrast, NE levels in the thalamushypothalamus, midbrain, cerebellum and pons-medulla were higher in SER and zitter rats at age 10–12 weeks than in age-matched tremor and Kyo:Wistar rats. Higher NE levels were also observed in midbrain, cerebellum, and pons-medulla of young SER as compared with young Kyo:Wistar rats. Turnover rates of NE were significantly lower in pons-medulla and cerebellum of the adult SER than in those of Kyo:Wistar rat. In genetic studies using backcross mating of zitter and BN rats, decreased DA was also observed in caudate nucleus of backcrossed zitter rats as compared with BN, F₁, and zitter wild-type rats. Increased NE contents were observed in the thalamus-hypothalamus, midbrain, and pons-medulla of zitter rats as compared with other rats, although the increase was also observed in the thalamus-hypothalamus and midbrain of zitter wild-type rats. Results suggest that a decrease in DA in caudate nucleus and an increase in NE in midbrain and pons-medulla are due to the homozygous zi gene, and together with previous findings, suggest that the decrease in DA, although probably not the only cause, facilitates appearance of tonic and absence-like seizures by lowering the threshold triggering such seizures.     

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 tuberinfundibular 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 DA in the anterior pituitary suggests in 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.     

Monoamine Levels and Turnover in Brain: Relationship to Priming Actions of Estrogen

Norepinephrine (NE), dopamine (DA) and serotonin (5HT) levels and turnover rates were studied in 8 discrete brain nuclei of ovariectomized rats 24 hours after the administration of 5 microgram of estradiol benzoate (EB) or sesame oil vehicle. This estrogen paradigm, by itself, did not induce sexual behavior or alter LH levels at the time these parameters were evaluated. However, combined with progesterone, the estrogen treatment was sufficient to generate an LH surge and induce sexual receptivity. Steady state concentrations of NE were significantly higher in the diagonal band of Broca (NDB) and the periventricular nucleus (PVE2; anterior hypothalamic level) following EB treatment. In addition, 5-hydroxyindole acetic acid (5HIAA) concentrations were elevated in the dorsal raphe of EB treated animals. Estrogen did not affect steady state concentrations of DA or 5HT in any of the brain nuclei studied. Turnover rates (K, pg/microgram protein/hr) and rate constants (k, hr-1) for NE were increased in the lateral septum (K, 140%; k, 120%), NDB (K, 160%; k, 130%) and the PVE2 (K, 140%; k, 70%) in EB treated animals. Estrogen decreased the rate constant for NE by 30% in the medial preoptic area. In contrast, DA and 5HT turnover rates were not significantly affected by estrogen. These results localize sites where estrogen induces changes in noradrenergic activity and suggest that these changes may be involved in the priming action of the steroid in inducing sexual behavior and/or gonadotropin secretion.     

Effects of amphetamine on catecholamine levels and turnover in discrete hypothalamic areas

The effects ofd-amphetamine (AMPH, 0.5 mg/kg, i.p.) on catecholamine (CA) levels and turnover in 5 discrete hypothalamic areas were examined using a sensitive radioenzymatic assay. Amphetamine, injected 10 or 45 min prior to sacrifice, produced little change in CA content of hypothalamic nuclei, except in the lateral perifornical area where dopamine (DA) content was significantly decreased, by 48%. The CA synthesis inhibitorα-methy-p-tyrosine (α-MpT, 300 mg/kg, i.p.), injected 3 h prior to sacrifice, produced a significant decline in DA (60–90%) and norepinephrine (NE, 20–80%) levels in most hypothalamic areas, whereas epinephrine (EPI) was only slightly affected. In α-MpT-pretreated rats, the impact of AMPH on the disappearance or turnover of hypothalamic CA was evaluated. The most dramatic effect was within the paraventricular nucleus, where AMPH significantly decrease NE and DA turnover, as reflected by an increase in the presence of these CA. In the dorsomedial nucleus, CA depletion appeared to be enhanced. These results demonstrate that, within the hypothalamus, the effects of AMPH on CA levels or turnover are anatomically localized, and that opposite effects on turnover may occur in nearby nuclei. The significance of these biochemical changes, relative to hypothalamically mediated behavioral effects of AMPH, is discussed.     

Clonidine effects on catecholamine levels and turnover in discrete hypothalamic and extra-hypothalamic areas

In rats treated with alpha-methyl-p-tyrosine (alpha-MpT) or saline, the effects of clonidine on the levels and turnover of norepinephrine (NE), epinephrine (EPI) and dopamine (DA) were analyzed in microdissected regions of the hypothalamus and extra-hypothalamic structures. In 7 of the 9 brain sites examined (namely dorsomedial nucleus, ventromedial nucleus, medial preoptic area, midlateral perifornical hypothalamus, frontal cortex, dorsal hippocampus and cerebellum), clonidine (50 micrograms/kg) caused a significant decrease in NE turnover, with no change in steady-state levels. In the two remaining areas, namely the hypothalamic paraventricular nucleus and the locus coeruleus, clonidine produced different patterns of effects. In the paraventricular nucleus (PVN), clonidine significantly reduced NE content in saline-treated rats, and in rats injected with alpha-MpT + clonidine, no further change in NE concentration was observed. In the locus coeruleus, both NE levels and turnover were unaltered. Epinephrine and DA turnover, in contrast to NE turnover, was unaffected by clonidine in all brain areas, with the exception of the midlateral hypothalamus, where the alpha-MpT-induced depletion of EPI and DA was totally reversed by clonidine, and in the frontal cortex, where DA turnover was also significantly reduced. These data are discussed relative to the proposed physiological actions of clonidine in the hypothalamus.     

Region-specific alterations in the concentrations of catecholamines and indoleamines in the brains of young and old F344 rats after L-deprenyl treatment

The effects of L-deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, on the concentrations of norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-hydroxytryptamine), and 5-hydroxyindoleacetic acid (5-HIAA) in medial basal hypothalamus (MBH), substantia nigra (SN), striatum (Str), and nucleus accumbens (NAc) of young (3 month) and old (21 month) male F344 rats were examined after a 7-day wash-out period following 1, 15, or 30 days of deprenyl treatment in young rats and a 9-day wash-out period after a 10-week deprenyl treatment in old rats. The brain areas were microdissected and the concentrations of neurotransmitters were measured by High Performance liquid chromatography with electrochemical detection (HPLC-EC). Deprenyl administration following the drug wash-out period increased the concentrations of DOPAC in the SN, Str, and in the NAc of young rats but it was decreased in the NAc of old rats. The concentration of HVA was lower in the Str of young deprenyl-treated rats, and in the Str and NAc of old deprenyl-treated rats, but it was higher in the SN of young deprenyl-treated rats. The concentration of 5-HIAA was increased in the MBH, SN, and in the NAc of young deprenyl-treated rats, but it was decreased in the Str and NAc of old deprenyl-treated rats. The concentration of NE was increased in the MBH, SN, Str, and in the NAc of young rats treated with deprenyl and in the MBH of old deprenyl-treated rats. The concentration of 5-HT was increased in the SN of young deprenyl-treated rats. The concentration of DA increased in the Str of both young and old deprenyl-treated rats. We concluded that a drug wash-out period after deprenyl treatment differentially affects the metabolism of catecholamines and indoleamine depending on the region of the brain and that this effect may be due to variation in the kinetics of MAO inhibition.     

Effects of suckling on serum prolactin levels and catecholamine concentrations and turnover in discrete brain regions

The effects of suckling on serum prolactin levels and catecholamine concentrations and turnover were examined in several discrete brain regions. Turnover rates were assessed by using the synthesis inhibitor alpha-methyltyrosine (alpha-MT) in combination with microdissection techniques for the removal of individual brain regions and sensitive radioenzymatic assays for norepinephrine (NE) and dopaime (DA). Prolactin secretion was induced by mothers experiencing 6 h of pup removal with subsequent pup replacement. Suckling or the administration of alpha-MT to mothers resulted in a marked increase in circulating titers of prolactin. A decrease in steady-state NE concentrations in the anterior hypothalamus and a decrease in steady-state DA concentrations in the ventromedial nucleus were noted in suckled mothers. The comparison of relative rates of NE depletion after alpha-MT treatment revealed a suckling-induced increase in turnover in the ventromedial nucleus and a suckling-induced decrease in turnover in the anterior hypothalamus. Neither suckling nor alpha-MT treatment produced any changes in NE or DA turnover rates in the arcuate nucleus or median eminence. These findings demonstrate that suckling-induced activation of prolactin results in changes in noradrenergic processes in the ventromedial and anterior hypothalamic nuclei. This suggests an involvement of noradrenergic systems in suckling-induced prolactin release.     

Effects of morphine on luteinizing hormone secretion and catecholamine turnover in the hypothalamus of estrogen-treated rats

This study examined the effects of morphine sulfate and naloxone alone or in combination on phasic luteinizing hormone (LH) secretion in estrogen-treated ovariectomized rats. Thereafter, the effects of morphine on initial concentrations, rate constants and rates of turnovers of norepinephrine and dopamine were evaluated in untreated or morphine-injected, estrogen-primed rats. Morphine, when given at 12.30 h, completely suppressed the spontaneous LH surges which occur in steroid-treated rats. The opiate antagonist, naloxone, (12.15 h) markedly amplified and advanced the time of LH release and a combination of morphine and naloxone produced peak afternoon LH values which were intermediate between those obtained in controls and in rats receiving only naloxone. Norepinephrine (NE) and dopamine (DA) turnover were calculated from data obtained in groups of rats sacrificed 0,45 or 90 min after administering 300 mg/kg b. wt. i.p. ofα-methyl-p-tyrosine (α-MPT) at 10.00 or 15.00 h. In these experiments, the medial preoptic nucleus (MPN) and the median eminence (ME) were microdissected and analyzed for changes in NE and DA concentrations by a radioenzymatic procedure. In estrogen-treated rats, NE rate constants and turnover significantly increased at 15.00 vs 10.00 h in MPN and ME concomitant with increases in serum LH. Morphine blocked both increases in rate constants and turnover in the MPN and ME and also significantly reduced initial concentrations of NE in the MPN. None of the DA parameters measured in MPN or ME changed in estrogen-treated controls between morning and afternoon. Further, while morphine did not affect DA turnover in the MPN, DA turnover declined in the ME. These data add to accumulating evidence which demonstrates an important modulatory role for hypothalamic opiate neurons in regulating catecholamine activity and gonadotropin secretion.     

Alterations in monoamines level in discrete brain regions and other peripheral tissues in young and adult male rats during experimental hyperthyroidism

The present study was conducted to investigate the effect of experimentally-induced hyperthyroidism on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats (60 rats of each age). Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T₄, 500 μg/kg body wt.) for 21 consecutive days. Induction of hyperthyroidism caused a significant elevation in DA and 5-HT levels in most of the tissues studied of both young and adult animals after 7, 14, and 21 days. NE content significantly decreased after 21 days in most of the brain regions examined and after 14 and 21 days in blood plasma of young rats following hyperthyroidism. In adult rats, NE content decreased after 14 and 21 days in cardiac muscle and after 21 days only in adrenal gland. It may be suggested that the changes in monoamines level induced by hyperthyroidism may be due to disturbance in the synthesis, turnover and release of these amines through the neurons impairment or may attributed to an alteration pattern of their synthesis and/or degradative enzymes or changes in the sensitivity of their receptors     

Turnover and synthesis of biogenic amines in discrete brainstem nuclei of the rabbit

By use of a microtechnique and sensitive enzymatic isotopic assays norepinephrine (NE), dopamine (DA) and serotonin (5-HT) turnover rates were measured in 6 discrete brainstem regions. The results from young (3 days) and adult (1 year) rabbits were compared. In the dorsal raphe nucleus (dr) of the younger animals the slopes of disappearance of NE and 5-HT were significantly higher than in the adults. Whereas, in the dr the slope of the decline of DA was found to be significantly lower in younger animals. In the dr turnover rates of NE and 5-HT were higher in the young animals. However, higher turnover rates for DA were seen only in the LC-A6 region. The young animals had significantly lower turnover times for NE and 5-HT in the dr. The nts was the only nuclear group to reach significance for DA, and the young animals had longer turnover times when compared to adults. These results are indicative of the different roles the neurotransmitter systems play in maintaining homeostasis. The delicate balances in these systems in the brains of younger animals may contribute to their increased susceptibility to perturbations.     

Involvement of GABA in the feedback action of estradiol on gonadotropin and prolactin release: Hypothalamic GABA and catecholamine turnover rates

The concentrations and turnover rates of norepinephrine (NE), dopamine (DA) and γ-aminobutyric acid (GABA) were measured in discrete brain areas of diestrous (D), proestrous (P), ovariectomized (OVX) and ovariectomized rats treated with estradiol-benzoate (EB) 12 or 24 h before decapitation. The turnover of NE in the medial preoptic area (MPO) correlates well with plasma LH levels under all endocrine conditions showing high NE turnover in P and OVX and low NE turnover in D and OVX-EB animals. The DA turnover shows no hormone-dependent changes in the MPO. In those animals where estrogens exert no (OVX) or a negative feedback action (D, OVX-EB) on LH the GABA turnover correlates inversely with LH and preoptic NE turnover showing low GABA turnover values in OVX and high values in D and OVX-EB. For P animals the inverse correlation cannot be confirmed. It is concluded that GABA mediates the negative feedback action of estrogens to LH-RH perikarya located in the MPO. GABA might act by presynaptic inhibition of NE axon terminals. This hypothesis is supported by morphological findings which indicate that axon terminals in the MPO are in close contact without separating glial lamellae.In the anterior mediobasal hypothalamus (AMBH) NE turnover correlates best with serum prolactin levels being high in P and OVX animals 24 h after EB treatment. The DA turnover is increased in OVX rats 24 h after EB. It is not yet clear if this increase might be a consequence of the elevated prolactin levels. GABA turnover in the AMBH shows no significant changes.GABA concentrations and turnover rates were also determined in the mediocortical amygdala where estrogen receptors have been reported and in the nucleus accumbens. No significant changes could be observed in these regions.     

Activity Wheel Running Reduces Escape Latency and Alters Brain Monoamine Levels After Footshock

We examined the effects of chronic activity wheel running on brain monoamines and latency to escape foot shock after prior exposure to uncontrollable, inescapable foot shock. Individually housed young (∼50 day) female Sprague-Dawley rats were randomly assigned to standard cages (sedentary) or cages with activity wheels. After 9–12 weeks, animals were matched in pairs on body mass. Activity wheel animals were also matched on running distance. An animal from each matched pair was randomly assigned to controllable or uncontrollable inescapable foot shock followed the next day by a foot shock escape test in a shuttle box. Brain concentrations of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) were assayed in the locus coeruleus (LC), dorsal raphe (DR), central amygdala (AC), hippocampus (CA1), arcuate nucleus, paraventricular nucleus (PVN), and midbrain central gray. After prior exposure to uncontrollable foot shock, escape latency was reduced by 34% for wheel runners compared with sedentary controls. The shortened escape latency for wheel runners was associated with 61% higher NE concentrations in LC and 44% higher NE concentrations in DR compared with sedentary controls. Sedentary controls, compared with wheel runners, had 31% higher 5-HIAA concentrations in CA1 and 30% higher 5-HIAA concentrations in AC after uncontrollable foot shock and had 28% higher 5-HT and 33% higher 5-HIAA concentrations in AC averaged across both foot shock conditions. There were no group differences in monoamines in the central gray or in plasma prolactin or ACTH concentrations, despite 52% higher DA concentrations in the arcuate nucleus after uncontrollable foot shock and 50% higher DOPAC/DA and 17% higher 5-HIAA/5-HT concentrations in the PVN averaged across both foot shock conditions for sedentary compared with activity wheel animals. The present results extend understanding of the escape-deficit by indicating an attenuating role for circadian physical activity. The altered monoamine levels suggest brain regions for more direct probes of neural activity after wheel running and foot shock.     

Corticosterone-dependent alterations in utilization of catecholamines in discrete areas of rat brain

This study investigated the impact of chronic adrenalectomy (ADX), and subsequent corticosterone (CORT) replacement to ADX rats, on brain levels of norepinephrine (NE) and dopamine (DA) and their extent of depletion after -methyl-p-tyrosine (-MpT) administration. Seven discrete hypothalamic areas, namely, the paraventricular nucleus (PVN), medial preoptic nucleus (POM), dorsomedial nucleus (DMN), ventromedial hypothalamus (VMH), perifornical lateral hypothalamus (PLH), supraoptic nucleus (SON), and arcuate nucleus/median eminence (ARC-ME), were examined. The steady-state content of NE and DA in all areas remained essentially unaltered 7 days after ablation of the adrenal glands, as well as after subsequent CORT replacement therapy in ADX rats. However, ADX, which reduced circulating CORT levels to 0.3 μg% as compared to > 3.0 μg% in sham rats, caused a significant increase in the depletion of NE following -MpT treatment, in 4 out of the 7 brain sites examined (PVN, PLH, DMN and ARC-ME). In these brain sites, the NE turnover rate (K,pg/μg protein/h) and rate constant (K,h⁻¹) increased following ADX. The chronic subcutaneous CORT implant (200 mg), which raised circulating CORT levels of ADX rats to 11 μg%, prevented this enhancement of NE turnover in the PVN, PLH and ARC-ME, but not the DMN. Unlike NE, DA utilization in the 7 discrete hypothalamic areas of -MpT-treated rats remained unaltered after ablation of the adrenal glands, as well as after the CORT replacement therapy in ADX rats. These results indicate that circulating CORT may have a modulatory role in the regulation of NE in specific discrete hypothalamic areas, and thereby have an impact on the control of various physiological responses.     

Contribution of noradrenergic neurons to 3,4-dihydroxyphenylacetic acid concentrations in the regions of the rat brain containing incertohypothalamic dopaminergic neurons

The purpose of this study was to determine the source of 3,4-dihydroxyphenylacetic acid (DOPAC) in medial zona incerta (MZI) and dorsomedial nucleus (DMN), with the overall aim of ascertaining whether alterations in the concentration of this dopamine (DA) metabolite reflect the activity of incertohypothalamic dopaminergic neurons. In both the MZI and DMN, the concentration of norepinephrine (NE) exceeds that of DA, reflecting a higher density of noradrenergic vs. dopaminergic neurons in these brain regions. The ratio of DOPAC to DA was greater than the ratio of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) to NE indicating that the activity of dopaminergic neurons in the MZI and DMN is greater than that of noradrenergic neurons. Destruction of noradrenergic neuronal axons in the ventral bundle following bilateral injections of the neurotoxin 5-amino-2,4-dihydroxy-alpha-methylphenylethylamine (5-ADMP) decreased NE concentrations in the MZI and DMN, but had no effect on the concentrations of DA or DOPAC, revealing that under basal conditions noradrenergic neurons contribute little to DOPAC concentrations in these brain regions. The DA receptor antagonist haloperidol increased, while the DA receptor agonist apomorphine decreased DOPAC concentrations in the MZI and DMN, indicating that alterations in the activity of incertohypothalamic dopaminergic neurons are accompanied by corresponding changes in the concentration of this DA metabolite. On the other hand, activation of noradrenergic neurons following administration of the alpha 2-adrenergic receptor antagonist idazoxan increased DOPAC concentrations in both the MZI and DMN in intact, but not in ventral bundle-lesioned rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ontogeny of tyrosine hydroxylase and dopamine-beta-hydroxylase activity in discrete limbic and hypothalamic structures of female rats

Tyrosine hydroxylase (TOH) and dopamine-ß-hydroxylase (DBH) activities were measured in the mediocortical amygdala (AMY), hippocampus (HPC), nucleus accumbens (ACB), medial preoptic area (MPO), and anterior and posterior parts of the mediobasal hypothalamus (AMBH and PMBH) in female rats of various postnatal ages. Serum LH, FSH and prolactin levels were also measured. In a previous study it was shown that dopamine (DA) and norepinephrine (NE) turnover rates in the MPO and the MBH increase between days 20 and 30 after birth and decrease thereafter. The cause for increased DA turnover was shown to be increasing serum prolactin levels. The activity of TOH in the ACB, MPO, AMBH and PMBH did not parallel DA turnover rates. Around day 20 after birth, when serum prolactin levels and preoptic and hypothalamic DA turnover increase, TOH activity also increased in the ACB and PMBH. In adult, diestrous animals, however, which have low serum prolactin levels and low preoptic and hypothalamic DA turnover, TOH activity was higher than in immature rats. The activity of DBH in the MPO, AMBH, AMY and HPC was high in 15-day-old animals, decreased between days 20 and 30 and then increased again to adult values. This pattern is just opposite to the one observed for serum prolactin levels and for preoptic and hypothalamic NE turnover. It is concluded that activity of both enzymes is not a good measure for neuronal activity of those NE and DA cells which innervate limbic and hypothalamic structures.     

Chronic hyperprolactinemia causes progressive changes in hypothalamic dopaminergic and noradrenergic neurons

Studies were undertaken to evaluate the effects of chronic hyperprolactinemia (HYP) on catecholamine concentrations and turnover rates in brain regions of the female rat. HYP was induced by inoculation of tissue derived from the prolactin secreting MtTW15 tumor. When serum prolactin (PRL) levels were moderately elevated, medial basal hypothalamus (MBH) dopamine (DA) turnover was enhanced and DA concentrations were moderately reduced. Later, as serum PRL levels increased to greater than 10 micrograms/ml, DA concentrations were further reduced and DA turnover was concomitantly reduced to below pre-tumor levels. In the preoptic area-anterior hypothalamus (POA-AH), DA concentrations were reduced as PRL levels increased and this was associated with a reduction in DA turnover. Between 5 and 8 weeks of tumor growth, DA turnover remained low, but DA concentrations increased. In the neurointermediate lobe of the pituitary (NIL) the tumor reduced DA turnover at 5 weeks only. Norepinephrine (NE) turnover, but not concentration, was reduced in both the POA-AH and MBH. Surgical removal of the tumor at 5 weeks of growth reduced serum PRL levels to near normal, but MBH DA concentrations and turnover remained depressed while POA-AH and NIL DA levels and turnover increased. Despite removal of the tumor, NE turnover remained depressed in both the MBH and POA-AH. These studies indicate that severe chronic HYP causes progressive alterations in hypothalamic catecholamine neurons which are not reversed by normalization of serum PRL levels. These results suggest that chronic HYP can cause long-lasting effects on some DA and NE neuronal systems.     

Regional differences in catecholamine formation and metabolism in the rat spinal cord

Catecholamine metabolism was assessed from the content of norepinephrine (NE), dopamine (DA) and their metabolites in various regions of the rat spinal cord during steady-state conditions and following treatment with alpha-methyl-p-tyrosine. The content of NE was rather uniform along the cord while DA was higher in the rostral portion of the cord than in the caudal portion.For both NE and DA there was a rostrocaudal decrease of their turnover rates along the cord. In the cervical cord, DA was formed at a faster rate than NE. There was no correlation between the content of catecholamine metabolites and amine turnover rates. The non-uniformity of catecholamine turnover in the cord probably arises from the fact that different regions of brain project to different regions of cord, each having a specific physiological function. Furthermore, our study provides added support for the presence of an independent DA-containing neuronal system in the spinal cord.