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K E Moore

Publications and source records attributed to K E Moore.

At least 199 records · Page 11Linked to original sources

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.

Aging↗

Influence of prolactin on dopaminergic neuronal systems in the hypothalamus.

The release of prolactin from the anterior pituitary is tonically inhibited by dopamine (DA), which is released from terminals of tuberoinfundibular neurons. These nerves, which originate in the mediobasal hypothalamus and terminate in the external layer of the median eminence, differ from other DA nerves in the brain in that they: 1)lack a high affinity DA uptake mechanism, 2) are not responsive to the acute administration of DA agonists or antagonists, 3) are responsive to increased concentrations of prolactin in blood or cerebrospinal fluid. The activity of different DA neuronal systems in the rat brain was estimated in terminals of these nerves by measuring: 1) the rate of decline of DA after the administration of a tyrosine hydroxylase inhibitor, alpha-methyltyrosine, or 2) the rate of accumulation of dopa after the administration of a decarboxylase inhibitor, NSD 1015. Systemic or intracerebroventricular injections of exogenous prolactin selectively increased the activity of tuberoinfundibular DA nerves. Furthermore, pharmacological manipulations that increased serum concentrations of endogenous prolactin (injections of DA antagonists or estrogen) also increased activity of tuberoinfundibular DA nerves. The prolactin-induced increases in tuberoinfundibular nerve activity were first noted 12-16 h after the prolactin concentrations increased. These results suggest that prolactin can exert a sluggish control over its own release by activating the tuberoinfundibular DA nerves that normally inhibit the release of this hormone.

Animals↗

Effects of intranigral administration of dopamine agonists and antagonists and baclofen on concentrations of dopac and dopamine in the striatum and substantia nigra of the rat.

Systemic administration of haloperidol to rats failed to alter the concentration of dopamine but increased the concentration of 3,4-dihydroxy-phenylacetic acid (DOPAC), the major metabolite of dopamine, in both the striatum and substantia nigra. These haloperidol-induced changes in DOPAC were prevented by an intranigral microinjection of baclofen, a drug which reduces nigrostriatal dopaminergic neuronal activity. It has been proposed that nigrostriatal neurons are regulated, in part, by the activation of autoreceptors in substantia nigra. However, intranigral microinjections of high concentrations of several dopaminergic antagonists failed to mimic the biochemical effects resulting from systemic administration of these drugs; instead, they slightly increased the concentrations of both dopamine and DOPAC in the striatum and decreased dopamine in substantia nigra. Intranigral microinjections of the dopamine agonist, apomorphine, failed to alter the concentration of DOPAC in the striatum, but reduced both dopamine and DOPAC in the nigra. If DOPAC concentrations reflect nigrostriatal dopaminergic neuronal activity, the present results suggest that dopaminergic agonists and antagonists acting in substantia nigra do not exert a major influence on the activity of these neurons.

3,4-Dihydroxyphenylacetic Acid↗

Dopa accumulation is a measure of dopamine synthesis in the median eminence and posterior pituitary.

A radioenzymatic assay was employed to measure the accumulation of DOPA in a variety of rat brain tissues 30 min after the administration of a decarboxylase inhibitor in order to estimate the activity of dopamine (DA) nerves which terminate in these regions. In the median eminence and posterior pituitary the accumulation of DOPA appears to occur primarily in DA nerves since: (1) the rate of synthesis of norepinephrine (NE), as estimated from the alpha-methyltyrosine-induced decline of catecholamines, accounts for less than 10% of total catecholamine synthesis in these two brain regions; and (2) the accumulation of DOPA is not significantly altered when the NE concentrations in these regions are reduced to 40--50% of control by prior intraventricular injections of 6-hydroxydopamine. These results suggest that the accumulation of DOPA in the median eminence and the posterior pituitary can be used to estimate the activity of tubero-infundibular and tuberohypophyseal DA nerves, respectively.

Animals↗

Comparison of dopamine synthesis regulation in the terminals of nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophyseal neurons.

The rate of accumulation of DOPA after the administration of decarboxylase inhibitor (NSD 1015) was determined in the striatum, olfactory tubercle, median eminence and posterior pituitary of the rat brain in order to obtain an index of the rate of synthesis of dopamine (DA) in the terminals of nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophyseal neurons, respectively. In all brain regions an increase in the concentration of DA by the administration of a monoamine oxidase inhibitor decreased DOPA accumulation while a decrease in the concnetration of DA by the administration of reserpine increased DOPA accumulation. These results indicate that end product inhibition plays a role in regulating DA synthesis in all four neuronal systems. Injections of DA agonists decreased and DA antagonists increased the accumulation of DOPA instriatum, olfactory tubercle and posterior pituitary, but not in median eminence. The administration of gamma-butyrolactone (GBL) and baclofen increased the concentration of DA and the accumulation of DOPA in the striatum, olfactory tubercle and posterior pituitary, and these effects were reversed by the administration of apomorphine. On the other hand, GBL and baclofen had no effect on the concentration of DA or the accumulation of DOPA in the median eminence. These two drugs did, however, reduce the alpha-methyltyrosine-induced decline of DA in the median eminence suggesting that they inhibit the activity of tuberoinfundibular nerves just as they do DA nerves in other systems. These results suggest that the regulation of DA synthesis in terminals of nigrostriatal, mesolimbic and tuberohypophyseal nerves is different from that in tuberoinfundibular nerves in that the latter nerves appear to lack an autoreceptor regulatory mechanism.

4-Butyrolactone↗

Destruction of dopaminergic nerve terminals in nucleus accumbens: effect on d-amphetamine self-administration.

Control rats initiate self-administration of d-amphetamine and achieve stable injection rates within 7-10 days. Rats in which dopamine nerve terminals in nucleus accumbens were destroyed by bilateral microinjections of 6-hydroxydopamine (6-OHDA) did not initiate self-administration of d-amphetamine when tested for as long as 19 days. In rats previously trained to self-administer d-amphetamine, 6-OHDA injections into nucleus accumbens abolished d-amphetamine self-administration. These results suggest that dopaminergic nerve terminals in nucleus accumbens are necessary for both the acquisition and maintenance of d-amphetamine self-administration.

Animals↗

Detection of preservatives in pharmaceutical and cosmetic products using agar gel electrophoresis.

A method is described using high voltage agar gel electrophoresis for the separation and microbiological detection of preservatives in pharmaceutical and cosmetic products. The positions of the preservatives were detected as zones of inhibition of a test organism within the nutrient agar gel and can be characterised by their migration, shape and presence of a halo. A wide range of preservatives commonly used in pharmaceutical and cosmetic preparations could be detected in low concentrations. The method however was not suitable for certain volatile preservatives and many primarily antifungal compounds could be detected above their use concentration.

Cosmetics↗

Comparative effects of penfluridol on circling behavior and striatal DOPAC and serum prolactin concentrations in the rat.

A single s.c. injection of penfluridol (3 mg/kg) to rats elevated serum concentrations of prolactin for more than 96 h whereas it increased striatal concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and inhibited apomorphine-induced circling behavior for less than 48 h. The dose of penfluridol needed to elevate serum concentrations of prolactin (0.1 mg/kg) was less than that required to elevate striatal concentrations of DOPAC (1 mg/kg) or inhibit apomorphine-induced circling (3 mg/kg). Furthermore, the penfluridol-induced increase of striatal DOPAC was more susceptible to reversal by apomorphine than was the increase of serum prolactin concentrations. These results suggest that the dopamine receptors in the pituitary, which are normally activated by dopamine released from tuberoinfundibular neurons, are more sensitive to the blocking actions of systemically administered penfluridol than are dopamine receptors in the striatum.

3,4-Dihydroxyphenylacetic Acid↗