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D C German

Publications and source records attributed to D C German.

At least 91 records · Page 5Linked to original sources
PubMed1981

Midbrain dopamine neurons: differential responses to amphetamine isomers.

Intravenously administered D- and L-amphetamine have different potency ratios in reducing the firing rates of dopamine cells in the substantia nigra and in the ventral tegmental area. While D-amphetamine is considerably more potent than L-amphetamine in reducing ventral substantia nigra dopamine neuronal impulse flow, D- and L-amphetamine are of similar potency in reducing dorsal substantia nigra and ventral tegmental dopamine neuronal impulse flow. These results suggest that all dopamine cell groups are not pharmacologically identical and that different dopamine nuclei may respond differently to psychoactive drugs. The comparable potencies of the D- and L-isomers on dorsal substantia nigra and ventral tegmental area dopamine neurons may explain, by a dopamine mechanism, the finding that comparable doses of the isomers produce schizophrenic-like symptoms.

Amphetamine↗
PubMed1981

Effects of severe dopamine depletion on dopamine neuronal impulse flow and on tyrosine hydroxylase regulation.

Reserpine depletes dopamine (DA) levels and increases tyrosine hydroxylase (TH) activity in the rat corpus striatum. TH is activated not only by enhancement of DA neuronal impulse flow, but also by cessation of impulse flow. To assist in the understanding of the relative contribution of impulse flow to the regulation of TH activity in the DA depleted neuron, we examined the consequences of severe DA depletion on substantia nigra DA neuronal impulse flow and on in vivo TH activity in the rat corpus striatum. One day after reserpine or 30 min after the reversible reserpine-like compound, Ro4-1284, striatal DA levels were severely depleted and in vivo TH activity was enhanced about three-fold. DA depletion was found to significantly increase DA neuronal impulse flow. Although the DA neuron is firing faster than normal in the DA depleted rat, because there is no DA being released it is still not clear whether the elevation in TH activity is due to the enhancement of impulse flow or to the lack of DA at presynaptic receptor sites, or both. gamma-Butyrolactone (GBL), causes a cessation of DA neuronal impulse flow and activates TH by a presynaptic autoreceptor mechanism. GBL inhibited by over 50 percent the elevation in TH activity produced by severe DA depletion. This finding suggests that the enhanced TH activation after DA depletion in in large part due to increased DA impulse flow. Furthermore, the TH activity seen with GBL in DA depleted rats was significantly less than that seen after GBL administration in normal rats. This finding is consistent with the hypothesis that the DA storage granule also plays a role in TH regulation.

4-Butyrolactone↗
PubMed1981

Catecholamine fluorescence and tissue culture morphology. Technics in the diagnosis of neuroblastoma.

Neuroblastoma is often confused histologically with other small round cell tumors such as Ewing's sarcoma, acute lymphocytic leukemia, lymphoma, and oat cell carcinoma, particularly at metastatic sites. Studies were performed to evaluate glyoxylic acid-induced catecholamine fluorescence as a rapid method for identifying neuroblastoma cells in biopsy specimens. The morphology of tumor explants in tissue culture was also evaluated for use as a diagnostic aid. Eighteen neuroblastomas were stained for catecholamines; 78% showed specific catecholamine fluorescence. Two ganglioneurons and a pheochromocytoma also showed positive catecholamine fluorescence. All 20 neuroblastomas placed in tissue culture demonstrated neurite outgrowth, a property that distinguishes neuroblastoma from other small round cell neoplasms. Seventeen nonneuroblastoma tumors displayed neither specific fluorescence nor neurite outgrowth. The ability of these two technics to identify neuroblastoma was compared with routine histology, urinary vanillylmandelic acid (VMA) spot tests, quantitative urinary VMA and catecholamine assays, and electron microscopy. Only electron microscopy was as sensitive as fluorescence and morphology in culture. The fluorescence method is rapid and simple and provides a valuable tumor marker when positive. Neurite outgrowth in cell culture and electron microscopy, although more time-consuming, were the most sensitive of all the diagnostic methods evaluated.

Adult↗
PubMed1980

Effects of chronic desipramine treatment on rat brain noradrenergic responses to alpha-adrenergic drugs.

It has been previously reported that long-term tricyclic antidepressant treatment in the rat causes a subsensitivity of central beta-receptor-stimulated adenylate cyclase along with alterations of brain norepinephrine (NE) content and metabolism. We have confirmed earlier findings that after one week of desipramine treatment (5.0 mg/kg b.i.d.) brain NE levels decline while NE metabolism is similar to control animals, but is above control after 12 days of treatment. Single cell recordings from noradrenergic neurons of the locus coeruleus (LC) show that after one week of desipramine treatment, neuronal firing rate is lower than in control rats but greater than that seen in response to acutely administered drug. Furthermore, desipramine injection in a dose which profoundly altered LC impulse flow in control rats produced little or no effect on impulse flow in chronically treated rats. Of 25 or 250 microgram/kg doses of clonidine, which are equieffective for decreasing brain NE metabolism in control animals, only the larger dose decreased NE metabolism in 12 day desipramine-treated rats. The postsynaptic alpha-antagonist prazosin (5.0 mg/kg) increased NE metabolism in both groups. These results suggest that presynaptic (alpha 2) adrenoreceptors become subsensitive during long-term desipramine treatment, thus allowing recovery of noradrenergic impulse flow in the presence of NE uptake inhibition.

Adrenergic alpha-Agonists↗
PubMed1980

Pimozide: delayed onset of action at rat striatal pre- and postsynaptic dopamine receptors.

It has been reported that the antipsychotic drug, pimozide, is unique in that it blocks postsynaptic dopamine (DA) receptors, but not presynaptic DA receptors. This was examined by comparing pimozide with haloperidol for time of onset of action in several experimental paradigms designed to demonstrate blockade of pre- and postsynaptic striatal DA receptors. Haloperidol (1.0 mg/kg s.c.) caused near maximum catalepsy scores within 90 min after injection, a time when twice as much pimozide had yet to produce catalepsy. Pimozide consistently exhibited a delayed onset of action on several dopaminergic biochemical parameters including: increased striatal DA metabolism, increased DA receptors. In electrophysiological studies, pimozide did not block the ability of apomorphine to inhibit DA impulse flow if given 5 to 10 min before apomorphine, but was effective if longer pretreatment times were allowed. These data indicate that a delay or pimozide action occurs at both postsynaptic and presynaptic DA receptors. It is known that pimozide binds with high affinity to neuroleptic binding sites (in vitro) and rapidly enters the brain after systemic injection. Pretreatment of animals with SKF 525-A, an inhibitor of liver mixed-function oxidase enzymes, had little or no effect on pimoxide's actions, suggesting that formation of an active metabolite is not the cause of pimozide's delayed actions. The reason for the delayed action is unclear, but pimozide will interact with both pre- and postsynaptic DA receptors if given sufficient time.

Animals↗
PubMed1979

Electrophysiological and biochemical responses of noradrenergic neurons to a non-amphetamine CNS stimulant.

Amfonelic acid (AFA), a potent non-amphetamine CNS stimulant, has been shown previously to have marked effects on dopamine (DA) metabolism and DA neuronal activity, but no effect on norepinephrine (NE) metabolism. AFA is known to inhibit the NE neuronal uptake mechanism. Other NE uptake inhibitors, such as desipramine (DMI), have been shown to decrease the firing rate of NE-containing locus coeruleus (LC) neurons. The purpose of the present study was to compare the actions of AFA and DMI electrophysiologically on LC neurons, and biochemically on NE metabolism in whg rate, with DMI being more potent. Brain NE metabolism was not influenced by either AFA or DMI at doses considerably higher than those which were effective in reducing NE neuronal impulse flow. Thus, NE uptake inhibition coupled with a decrease in impulse flow results in no net change in NE metabolite formation. The effects of AFA on LC unit activity do not seem to be due to its marked effects on brain DA, since DA receptor blockade with haloperidol had little effect on LC unit responsiveness to AFA (or amphetamine). Whereas AFA has dramatic effects on DA metabolism via enhanced release per impulse, the drug has minimal effects on NE metabolism, and this specificity of action may be related to differences in NE and DA transmitter storage mechanisms. It is concluded that the effects of AFA on NE neuronal firing rate are likely due to the drug's DMI-like action and not to enhanced NE release per impulse.

Animals↗
PubMed1979

Dopaminergic neuronal responses to a non-amphetamine CNS stimulant.

The present study compares the effects of d-amphetamine (d-AMP) and the potent non-amphetamine CNS stimulant, amfonelic acid (AFA), on the firing rate of single midbrain dopaminergic (DA) neurons and on neostriatal DA metabolism (dihydroxyphenylacetic acid--DOPAC). The results indicate that AFA, like d-AMP, reduces the firing rate of DA neurons, although unlike d-AMP, AFA does not cause a decrease in neostriatal DOPAC content and, in fact, enhances that produced by haloperidol (HALO). The AFA-induced decrease in firing rate, like d-AMP, is reversed by the DA receptor blocker HALO, but again unlike d-AMP, the decrease in firing rate is not prevented by catecholamine synthesis inhibition with alpha-methyl-para-tyrosine. Thus, both amphetamine and amfonelic acid have identical electrophysiological effects on DA neurons but act by different mechanisms.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1978

Anatomic and pharmacologic differences between two types of aversive midbrain stimulation.

Chronic stimulating electrodes were implanted into two separate midbrain sites in rats. One site was the dorsal central gray area (DCG), where electrical stimulation produced frantic, escape-seeking behavior which grossly appeared fear-like and/or pain-like. The other site was in the ventral reticular formation (VRF), where stimulation produced a stereotyped circling response. Stimulation at both sites was aversive in that these animals would bar press for escape in a decremental bar-pressing paradigm. In this paradigm, each bar press decremented the current by five per cent of the initial current level. Following the acquisition of stable baseline decremental bar-pressing performance, animals were given injections of either the serotonin-depleting drug, para-chlorophenylalanine (PCPA), or the catecholamine-depleting drug, alpha-methyl-para-tyrosine (AMPT). Control animals received normal saline. Compared to saline control animals, PCPA-injected DCG-stimulated animals showed a marked increase in decremental bar pressing, whereas VRF-stimulated animals showed no change. AMPT-injected VRF-stimulated animals showed a marked decrease in decremental bar pressing, but the DCG-stimulated animals were not affected. These results suggest that escape behavior from electrical stimulation of midbrain sites is mediated by more than one neural system.

Animals↗
PubMed1978

An autoradiographic, semistereotaxic mapping of major projections from locus coeruleus and adjacent nuclei in Macaca mulatta.

The autoradiographic method was used to trace projections from the monkey locus coeruleus (LC) and adjacent nuclei (nn. parabrachiales, n. tractus mesencephalicus nervus trigemini, substantia grisea centralis). Pathways attributed to LC are presented diagrammatically in a set of 26 coronal sections. They include a descending pathway along the tractus tegmentalis centralis, a caudal pathway entering the corpus medullaris cerebellaris via the lateral wall and roof of ventriculus quartus, and an ascending pathway along the tractus tegmentalis centralis giving off branches to the commissura posterior, tractus habenulo-interpeduncularis, centrum medianum and n. ventralis posteromedialis thalami, fasciculus lenticularis, lamina medullaris thalami lateralis, capsula interna, commissura supraoptica dorsalis, tractus supraoptico-hypophyseus, stria terminalis, laminae medullaris interna and medialis and pars interna of globus pallidus, corpus subfornicale, capsula externa, stria longitudinalis, cingulum, and gyrus rectus. A contribution to the branches entering n. ventralis posteromedialis thalami and the commissura supraoptica dorsalis was attributed to the nn. parabrachiaels. Axons entering trigeminal structures via the tractus mesencephalicus nervus trigemini were attributed to labeling of cells in the nucleus of that tract. Terminal areas attributed to labeling of LC axons were evident in decreasing order of density in the bed nucleus of stria terminalis, substantia innominata, nn. amygdalae anterior, centralis and basalis (dorsal portion), nn. paraventricularis, supraopticus and dorsomedialis hypothalami, and n. antero-ventralis thalami.

Animals↗
PubMed1978

Serotonergic reduction of dorsal central gray area stimulation-produced aversion.

Stimulating electrodes were implanted into the dorsal central gray area (DCG) of rats. The animals were trained to bar press to decrement the aversive DCG stimulation current. Rats treated with 5-hydroxytryptophan (5-HTP), 75 mg/kg or 150 mg/kg, showed a dose-dependent reduction in decremental bar pressing. In a second study, animals received either chlorimipramine, 15 mg/kg, protriptyline, 15 mg/kg, or 5-HTP, 150 mg/kg. Chlorimipramine, a strong blocker of serotonin reuptake, and 5-HTP produced significant reductions in decremental bar pressing. Protriptyline, a weak serotonin reuptake blocker, produced no significant effect. These results suggest that serotonin reduces aversive neural mechanisms associated with the dorsal central gray area.

5-Hydroxytryptophan↗