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Biomedical subjects

G R Hanson

Publications and source records attributed to G R Hanson.

At least 163 records · Page 9Linked to original sources
PubMed1986

Roles of D1 and D2 dopamine receptor subtypes in mediating the methamphetamine-induced changes in monoamine systems.

Previous studies have demonstrated that the effects of methamphetamine (METH) on dopaminergic and serotonergic systems are likely related to METH-induced increases in dopamine release. The ability of haloperidol to prevent these effects of METH suggests that dopamine receptor activation is involved in mediating these METH actions. The present studies were undertaken to determine what role the dopamine receptor subtype(s) might have in such METH effects. We found that the D1 antagonist, SCH23390, attenuated or blocked the effects of METH on dopaminergic and serotonergic systems, whereas the D2 antagonist, sulpiride, blocked the effects of METH on only the dopaminergic system. The results of the present studies suggest that METH-induced increases in dopaminergic action on both D1 and D2 receptors are associated with the effects of METH on the dopaminergic system. In contrast, dopamine action on D1, but not on D2, receptors appears to be involved in the effects of METH on the serotonergic systems of the neostriatum and the cerebral cortex.

Animals↗
PubMed1985

Studies on the mechanism of tolerance to methamphetamine.

We have reported that the ability of high doses of methamphetamine to impair dopamine and serotonin synthesis in the rat brain is attenuated when animals are pretreated with gradually increasing doses of methamphetamine. To examine the mechanism of this tolerance phenomenon, the effect of methamphetamine on several neurochemical parameters was determined in naive and methamphetamine-pretreated rats. The elevation of nigral substance P concentrations by methamphetamine was attenuated in pretreated compared to naive rats. The methamphetamine-induced reduction in [3H]sulpiride binding in the rat neostriatum and nucleus accumbens was similarly attenuated in animals pretreated with methamphetamine. Determination of brain concentrations of methamphetamine and amphetamine revealed significantly lower concentrations of both compounds in the brains of pretreated compared to naive animals. The results indicate a reduction in the ability of methamphetamine to increase dopamine transmission in the brains of methamphetamine-pretreated rats. Furthermore, this effect appears to be due, at least in part, to a change in the disposition of methamphetamine in pretreated animals.

Amphetamine↗
PubMed1985

Dopamine-mediated increases in nigral substance P-like immunoreactivity.

The results reported herein strongly suggest that increased dopaminergic and not increased serotonergic activity is responsible for methamphetamine-induced increases in the nigral concentration of substance P-like immunoreactivity (SPLI). Thus, treatment of rats with the specific dopamine (DA) uptake blockers amfonelic acid (AFA) and nomifensine caused elevations in the SPLI levels within the substantia nigra similar to that of methamphetamine (METH). In contrast, the specific serotonin uptake blockers citalopram and chlorimipramine were without significant effects on this substance P (SP) system. Additional studies revealed that the mechanisms whereby the DA uptake blockers and METH influence the striatonigral SP pathway are likely different. Specifically, AFA, unlike METH, altered the SP system without causing changes in the monoaminergic synthesizing enzymes tyrosine and tryptophan hydroxylase; in addition, pretreatment with reserpine abolished the AFA effect on nigral SPLI but did not interfere with METH-mediated changes in the SP system.

Animals↗
PubMed1985

Methamphetamine-induced depression of monoamine synthesis in the rat: development of tolerance.

Animals treated with high doses of amphetamines have been used as a model of schizophrenia due to the similarities between the psychosis associated with this mental disorder and that induced by chronic amphetamine abuse. When administered to naive rats in high doses, the amphetamine-like CNS stimulant methamphetamine produces drastic alterations in the neurochemical parameters of the neostriatal monoaminergic systems. These alterations are characterized by a decrease in the activities of the rate-limiting enzymes for dopamine and serotonin synthesis, as well as a decrease in the concentrations of both neurotransmitters and their metabolites. However, tolerance develops to these neurochemical effects when drug administration occurs in a pattern similar to that encountered during chronic amphetamine abuse. The results indicate that the neurochemical alterations produced by amphetamines in naive and tolerant animals differ widely. This suggests that the administration of high doses of amphetamine-like central stimulants to naive rats may not be an appropriate model for studying the neurochemical changes associated with psychosis and amphetamine abuse.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Role of dopamine in the neurotoxic effects of methamphetamine.

Multiple administrations of high doses of methamphetamine to rats cause long-term depression of both dopamine and serotonin synthesis. Coadministration of the catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine, antagonizes this effect of methamphetamine on both neurotransmitter systems. However, when catecholamine synthesis was maintained by the administration of L-dopa and the peripheral decarboxylase inhibitor R04-4602, alpha-methyl-p-tyrosine no longer prevented the effects of methamphetamine on either dopamine or serotonin synthesis. In addition, the administration of the specific dopamine uptake blocker, amfonelic acid, significantly attenuated the changes in the serotonin synthesizing enzyme, tryptophan hydroxylase, resulting from multiple high doses of methamphetamine. The ability of a single administration of methamphetamine to depress tryptophan hydroxylase was also dependent on catecholamine synthesis. These results suggest that dopamine plays an important role in the changes mediated by the administration of methamphetamine in both the dopaminergic and serotonergic systems.

Animals↗
PubMed1984

Opposite responses in the striato-nigral substance P system to D1 and D2 receptor activation.

The roles of different dopamine receptors in mediating the responses of the striato-nigral substance P (SP) feedback loop were investigated. Subacute treatment of rats with the D1 agonist, SK&F 38393, produced a significant decrease in SP content in the substantia nigra whereas treatment with the D2 agonist, RU 24926, elevated nigral SP concentrations. Consequently, the elevation in nigral SP content which occurs following treatment with methamphetamine is likely a D2-mediated event. This conclusion is supported by our observation that the D2 antagonist, sulpiride, totally blocked the methamphetamine effect. These findings suggest that D1 and D2 receptors mediate opposing influences on the SP feedback system.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1984

Increases of substance P-like immunoreactivity within striatal-nigral structures after subacute methamphetamine treatment.

Substantial increases in the nigral concentration of substance P-like immunoreactivity (SPLI) were observed after subacute administration of the indirect dopamine agonist, methamphetamine (METH, 15 mg/kg every 6 hr; five doses). The effect was opposite, and thus consistent, with the reduction of SPLI levels previously reported in nigral tissue after pharmacological blockade of the nigrostriatal dopaminergic activity. In addition, subacute METH treatment increased SPLI concentrations in other structures associated with the basal ganglia, such as the striatum and entopeduncular nucleus, but not in the hypothalamus or dorsal raphe nucleus. Subacute treatment with d-amphetamine exerted METH-like effects on the substance P neurons of the basal ganglia, whereas haloperidol completely antagonized the METH effect. The possibility that monoaminergic systems help mediate the response of the substance P system to subacute METH treatment is examined.

Animals↗
PubMed1982

Regulation of the proliferation of embryonic chick leptomeningeal cells in vitro by both contact inhibition and co-culture with CNS neurons.

Cultures of leptomeningeal cells (LMCs) isolated from the pia-arachnoid membrane of 10-day chick embryos were studied in order to elucidate the mechanisms which regulate the proliferation of these embryonic nonneuronal cells. Thymidine incorporation was quantified in LMC cultures of varying density and in co-cultures containing both LMCs and neurons. The following results were obtained. First, proliferation of LMCs was very sensitive to contact inhibition. Second, proliferation was also inhibited by co-culture of leptomeningeal cells with neurons isolated from either the cerebral hemispheres or optic lobes. Third, co-culture with sympathetic neurons isolated from the peripheral nervous system did not inhibit LMC proliferation; thus, the inhibition resulting from co-culture with neurons exhibits some regional specificity. Fourth, proliferation of the leptomeningeal cells was inhibited by addition of the sonicate of either cerebral neurons or LMCs but stimulated by addition of the sonicate of sympathetic neurons. The effect of addition of varying numbers of either intact or sonicated cerebral neurons on thymidine incorporation by cerebral glial cells was also examined. Addition of intact cerebral neurons stimulated cerebral glial proliferation at all concentrations. In contrast, addition of sonicate of cerebral neurons stimulated proliferation at low concentrations but inhibited it at high concentrations. Since addition of intact cerebral neurons inhibits the proliferation of leptomeningeal cells under the same conditions which stimulate the proliferation of cerebral glial cells, these neurons might play a complex role in orchestrating the proliferation of nonneuronal cells during development of the brain.

Animals↗
PubMed1982

Preparation and partial characterization of highly purified primary cultures of neurons and non-neuronal (glial) cells from embryonic chick cerebral hemispheres and several other regions of the nervous system.

Purified cultures of neurons and non-neuronal (glial) cells were prepared from the cerebral hemispheres of 10-day chick embryos by a method previously used for embryonic chick sympathetic ganglia 16. This technique separates these cell types on the basis of both: (1) differences in the adhesiveness of neurons and non-neuronal cells to a collagen substrate; and (2) the capacity of neurons to form homotypic aggregates. Purity of the cerebral non-neuronal cultures was determined to be greater than or equal to 99.5% by microscopic examination, while that of the cerebral neuronal cultures was only 92%. Modification of the technique by periodic redissociation of the neuronal aggregates during cell separation increased the purity of the neuronal cultures to greater than or equal to 97% as determined both by microscopic examination and by measurement of levels of butyrylcholinesterase, an enzyme present in the non-neuronal cells. Highly purified cultures of neurons were also prepared from the optic lobes of 10-day chick embryos (greater than or equal to 98%), but attempts to obtain non-neuronal cultures of reasonable density from this tissue were unsuccessful. In addition, highly purified non-neuronal cultures (greater than or equal to 99.5%) were prepared from the dorsal root ganglia of 12-day chick embryos, but cultures enriched with dorsal root neurons could only be partially purified (82%). Specific activity of butyrylcholinesterase in cerebral non-neuronal cells was found to vary inversely with the density of non-neuronal cells.

Animals↗
PubMed1982

Neuronal stimulation of non-neuronal (glial) cell proliferation: lack of specificity between different regions of the nervous system.

Purified and recombined primary cultures of neurons and non-neuronal (glial) cells were prepared from the cerebral hemispheres of 10-day chick embryos. Addition of cerebral neurons to homologous non-neuronal cultures stimulated incorporation of [3H]thymidine by 2.8-fold and increased the frequency of labelling of the non-neuronal cells by 3.5-fold as visualized by autoradiography. In contrast, cerebral neurons did not stimulate the proliferation of either embryonic chick fibroblasts or leptomeningeal cells. Furthermore, addition of either fibroblasts or extra non-neuronal cells did not stimulate non-neuronal cel proliferation. These data demonstrate for the first time that neurons isolated from the central nervous system can selectively stimulate the proliferation of homologous non-neuronal cells. Cell proliferation was also studied in cultures containing both homologous and heterologous combinations of neuronal and non-neuronal cells prepared from several different portions of the nervous system (cerebral hemispheres, optic lobes, sympathetic ganglia, and sensory ganglia). Addition of embryonic neurons stimulated non-neuronal cell proliferation in all cell combinations. Thus, neurons isolated from one region of the nervous system can stimulate the proliferation of non-neuronal cells isolated from other neural regions.

Animals↗
PubMed1981

Haloperidol-induced reduction of nigral substance P-like immunoreactivity: a probe for the interactions between dopamine and substance P neuronal systems.

Protracted blockade of dopamine receptors by haloperidol has been shown to cause a reduction in nigral content of substance P-like immunoreactivity (SPLI). This pharmacological effect is used to study the mechanisms whereby the dopaminergic and substance P systems interact. Data presented in this paper suggest that 1) blockade of dopamine postsynaptic receptors alters nigral SPLI levels associated with the substance P striatal-nigral loop, 2) destruction of the nigral-striatal dopaminergic pathway results in changes in nigral content of SPLI similar to that induced by haloperidol, 3) several weeks after nigral-striatal lesions, compensatory mechanisms mediate a return of nigral SPLI content to control levels and 4) substance P striatal-nigral circuits continue to respond to dopaminergic input after kainic acid lesions in the anterior striatum, whereas properly placed mechanical striatal-nigral lesions appear to be effective in preventing this interaction. The data support a dynamic role for striatal-nigral substance P fibers in the extrapyramidal circuitry and suggest that his pathway must be accounted for when studying the interactions of transmitter systems within this locomotor center.

Animals↗
PubMed1980

A comparison of two factors affecting the proliferation of non-neuronal (glial) cells in vitro.

Earlier studies have shown that the proliferation of sympathetic non-neuronal cells in vitro can be stimulated either by direct contact with growing neurons or by addition of sonicated neurons of the same type to the culture medium. Several lines of evidence presented herein suggest that intact neurons and neuronal sonicate probably stimulate [3H]thymidine incorporation by distinctly different mechanisms. First, mitogenic factors are present in sonicates of cell types (fibroblasts and non-neuronal cells) which do not stimulate non-neuronal cell proliferation when added as intact cells. Second, neuronal sonicate and intact neurons differ in the types of cells which are responsive to their mitogenic influence. Third, intact neurons do not appear to stimulate non-neuronal cell proliferation by the same mechanism as that of neuronal sonicate. Further similarities between stimulation of non-neuronal cell proliferation in vitro and reactive gliosis in vivo are discussed.

Animals↗
PubMed1980

Elevation of substance P-like immunoreactivity in rat central nervous system by protease inhibitors.

Several substance P-rich areas in rat CNS had increased levels of substance P-like immunoreactivity following the intraventricular injection of the protease inhibitors SQ 20881, SQ 14225, and leupeptin. There were significant differences in response patterns from region to region, possibly on account of an interaction of anatomical, biochemical, or physiological variables. Although the compound SQ 14225 appeared to be the most potent of the inhibitors examined, it had no apparent effect on CNS substance P-like immunoreactivity when administered peripherally.

Animals↗
PubMed1978

Stimulation of non-neuronal cell proliferation in vitro by mitogenic factors present in highly purified sympathetic neurons.

Sympathetic neurons have been demonstrated to contain one or more mitogens which are active on highly purified non-neuronal cells cultured in medium containing an optimal concentration of fetal calf serum. Neurons and homologous non-neuronal cells were separated by a method recently developed in this laboratory. The highly purified neurons were either sonicated or homogenized prior to addition to nonneuronal cultures. The presence of neuronal sonicate (1) greatly stimulated [3H]thymidine incorporation into acid-precipitable macromolecules without altering the soluble [3H]thymidine pool, (2) increased both the fraction of non-neuronal cells which took up [3H]thymidine and the density of labeling as observed by autoradiography, and (3) increased the number of cells present in treated cultures after 40 h. The enhancement of [3H]thymidine incorporation was dose-dependent and did not involve cyclic AMP. Addition of neuronal sonicate also caused marked non-neuronal cell elongation which resulted in the elaboration of very long cell processes. The active factor(s) in the neuronal sonicate were partially heat-labile. Norepinephrine was ruled out as a possible mitogenic factor.

Animals↗
PubMedDate not supplied

Comparison of responses by striatonigral substance P and neurokinin A systems to methamphetamine treatment.

Multiple administrations of high doses of methamphetamine (METH) previously have been shown to significantly elevate the concentrations of substance P-like immunoreactivity in CNS regions associated with the basal ganglia. Recently, another tachykinin, neurokinin A (NKA), has been found to be closely associated with substance P (SP). While both neuropeptides exert comparable effects when locally injected, there are significant differences in their potencies apparently based on the relative concentrations of their unique receptors. Due to the controversy which has arisen as to their respective roles within the basal ganglia, we have evaluated and compared the responses of the striatal and nigral SP and NKA systems to METH treatment. We observed that multiple high doses of this stimulant increased the nigral and striatal concentrations of both neuropeptides in an identical fashion. Our observation that METH treatment did not alter the relative concentrations of SP and NKA suggests that responses of both transmitter systems, associated with the basal ganglia, parallel each other and are sensitive to the same regulatory mechanisms.

Animals↗