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Biomedical subjects

G C Wagner

Publications and source records attributed to G C Wagner.

At least 91 records · Page 5Linked to original sources
PubMed1985

Age-dependent effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP).

The neurotoxic effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) have been shown to be dependent upon its conversion to 1-methyl-4-phenyl pyridine ion (MPP+) by monoamine oxidase. Since central monoamine oxidase activity increases with age, the neurotoxic effects of MPTP should be age-dependent. This hypothesis was evaluated by administering MPTP to three groups of rats differing in age. It was observed that both the lethality and neurotoxicity of MPTP were age-dependent.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Ascorbic acid reduces the dopamine depletion induced by MPTP.

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice was found to cause a long-lasting depletion of striatal dopamine concentrations, but did not alter striatal serotonin concentrations. The concomitant administration of ascorbic acid attenuated this MPTP-induced dopamine depletion. These observations are discussed in reference to the possible mechanisms through which MPTP exerts its neurotoxic actions on dopaminergic neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Target biting associated with a gustatory avoidance response.

Gustatory avoidance studies normally focus on the diminished occurrence of a consummatory behavior as the primary dependent variable. Several reports have described behaviors which accompany this gustatory avoidance response but no attempt has been made to automate collection of such data. In the following studies lithium chloride (LiCl) was administered to rats following saccharin consumption in a standard gustatory avoidance paradigm. The rats also had the opportunity to make noncontingent target biting responses on an inanimate target. It was observed that there was a significant decrease in saccharin intake following its pairing with LiCl. High target biting rates were associated with this avoidance response and, to a lesser degree, with initial target exposure. These observations are discussed in terms of paradigm contingencies.

Aggression↗
PubMed1985

Cocaine blocks the dopamine depletion induced by MPTP.

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice causes a long-lasting depletion of striatal dopamine. The concomitant administration of a dopamine uptake blocker, cocaine, protected the mice from this MPTP-induced dopamine depletion. These observations are discussed in reference to the mechanism through which MPTP enters dopaminergic neurons as well as species differences in the sensitivity of the serotonergic system to the toxic effects of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Pretreatment with ascorbic acid attenuates the neurotoxic effects of methamphetamine in rats.

The toxic effects of methamphetamine on dopamine and serotonergic neurons have recently been linked to the endogenous formation of 6-hydroxydopamine and 5,7-dihydroxytryptamine, respectively. It has been speculated that the ability of methamphetamine to both release dopamine and serotonin as well as to inhibit monoamine oxidase activity leads to the non-enzymatic oxidation of dopamine and serotonin to the neurotoxins. This hypothesis was evaluated by pretreating rats with high doses of an antioxidant (ascorbic acid) prior to the administration of methamphetamine. It was observed that the administration of 25.0 mg/kg of methamphetamine at 12 hour intervals for a four day period caused a long-lasting depletion of dopamine and serotonin. Pretreatment with 100.0 mg/kg of ascorbic acid 30 minutes before each methamphetamine injection significantly (but not completely) attenuated this neurotoxic action of methamphetamine. These observations are discussed in reference to animal models of Parkinson's disease.

Animals↗
PubMed1984

High-field, variable-temperature Mössbauer effect measurements on oxyhemeproteins.

We measured Mössbauer spectra of human oxyhemoglobin, its isolated beta chains, and of oxymyoglobin from horse and sperm whale in fields of 4 or 6 T between 4.2 and 200 K in order to characterize the electronic state of the oxyheme complex. Diamagnetic sodium nitroprusside measured under the same conditions served as a control. The spectra of all compounds are reproduced adequately by a model that assumes a diagmagnetic iron and treats the quadrupole splitting, the asymmetry parameter and the Mössbauer linewidth as adjustable parameters. The results provide no indication in the oxyhemeproteins of the excited triplet state that was postulated by Cerdonio and co-workers (Cerdonio, M., Congiu-Castellano, A., Mogno, F., Pispisa, B., Romani, G.L. and Vitale, S. (1977) Proc. Natl. Acad. Sci. USA 74, 398-400) on the basis of susceptibility measurements on oxyhemoglobin.

Humans↗
PubMed1984

Effects of phencyclidine, haloperidol, and naloxone on fixed-interval performance in rats.

Phencyclidine (PCP), haloperidol, and naloxone were administered alone and in combination to rats responding under a fixed-interval schedule for water presentation. Lower doses of PCP (0.25-2.0 mg/kg) and naloxone (0.001-0.1 mg/kg) produced increases while higher doses produced dose-dependent decreases in response rate. Haloperidol (0.0625-0.5 mg/kg) produced a monotonic dose-dependent decrease in responding. When a dose of naloxone (8.0 mg/kg) that did not alter responding was administered prior to the PCP, the PCP dose-response curve was shifted to 6.5-fold lower doses of PCP. When a dose of haloperidol (0.0625 mg/kg) that did not alter responding was administered prior to the PCP, the PCP dose-response curve was shifted to 1.5-fold higher dose of PCP. These observations are discussed in relation to current views of the mechanism of PCP action.

Animals↗
PubMed1984

Medial and lateral amygdalectomy differentially influences consummatory negative contrast.

Rats shifted from a 32% to 4% sucrose solution consume substantially less 4% sucrose than unshifted animals that experience only the 4% solution. This negative contrast effect was found to be attenuated by lesions of the lateral aspects of the amygdala (basolateral, lateral, and basomedial nuclei) and eliminated by lesions of the medial aspects of the amygdala (corticomedial and central nuclei). The results are discussed in terms of the possible role the amygdala may play in some of the proposed determining factors mediating consummatory negative contrast (e.g., emotionality, neophobia, memory).

Amygdala↗
PubMed1984

Interactions of naloxone and haloperidol with phencyclidine: effects on milk intake.

Phencyclidine (PCP), naloxone and haloperidol were administered alone and in combination to rats trained to drink sweetened-condensed milk during a 20 min daily session. PCP (1.0-16.0 mg/kg) produced a dose-dependent decrease in milk intake. All doses of naloxone (0.1-16.0 mg/kg) produced approximately a 30% decrease in milk intake. Haloperidol (0.125 mg/kg) had virtually no effect on milk intake. When a dose of naloxone which reduced milk intake by approximately 30% (8.0 mg/kg) was administered as a pretreatment to the PCP, the PCP curve was shifted to the left (lowered) to that degree. When haloperidol (0.125 mg/kg) was administered as a pretreatment to the PCP, the PCP dose-response curve was shifted 1.5 fold to the right. These interactions are similar to those observed in other behavioral paradigms and are discussed in reference to PCP's actions as an indirect dopaminergic agonist.

Animals↗
PubMed1984

Effects of methamphetamine on atropine-induced conditioned gustatory avoidance.

The repeated administration of high doses of methamphetamine (MA) has been shown to cause monoaminergic damage in rhesus monkeys and rats. In view of the purported interaction between central cholinergic and monoaminergic systems, rhesus monkeys and rats previously exposed to high doses of MA were tested in conditioned gustatory avoidance studies with atropine (a muscarinic blocker) as the unconditioned stimulus. It was observed that both rhesus monkeys and rats previously exposed to high doses of MA exhibited less of an atropine-induced avoidance than control monkeys and rats. To control for the nonspecific effects of prior exposure to stimulants, an additional group of rats previously exposed to high doses of methylphenidate ( a stimulant shown to not cause catecholaminergic damage) was tested in the same paradigm. The methylphenidate treated rats showed no change in sensitivity to atropine in the conditioned gustatory avoidance paradigm as compared to control rats which indicated that prior exposure to the nonspecific effects of a stimulant without monoaminergic alterations does not alter the sensitivity of atropine's avoidance-inducing properties. The results of these experiments imply that atropine's avoidance-inducing properties may in part be mediated through the monoaminergic system.

Animals↗
PubMed1984

Tolerance following the repeated administration of high doses of phencyclidine: no relation to central catecholamine depletion.

The tolerance which develops following the repeated administration of phencyclidine has been attributed to both pharmacological and behavioral adaptations. In the present study, the possibility that neurochemical alterations induced by the repeated administration of phencyclidine might account for some portion of the observed tolerance was examined. Specifically, it was postulated that the repeated administration of high doses of phencyclidine might result in long lasting depletion of central catecholamine stores and that this neurochemical perturbation might result in tolerance to the drug's effects. It was observed that phencyclidine disrupted the performance of rats on a fixed-interval schedule maintained by water presentation. The repeated administration of high doses of phencyclidine (but not of a comparable volume of saline) during a period when subjects were not engaged in the fixed-interval task resulted in the development of a long lasting tolerance, but this tolerance could not be accounted for in terms of a depletion of central catecholamine stores.

Animals↗
PubMed1983

Alpha-methyltyrosine attenuates and reserpine increases methamphetamine-induced neuronal changes.

The repeated administration of methamphetamine to rats has been shown to cause a long-lasting depletion of dopamine in various brain regions. In the first study, the effects of pretreatment with alphamethyltyrosine (AMT) or reserpine on the long-lasting methamphetamine-induced dopamine depletion were examined. In the second study, the effects of AMT and reserpine on central dopamine levels were measured in rats previously treated with methamphetamine. Pretreatment with AMT attenuated the long-lasting dopamine depletion induced by methamphetamine, whereas, pretreatment with reserpine increased the depletion. The acute effects of AMT and reserpine on brain dopamine were not altered when administered two weeks after the last methamphetamine injection.

Animals↗
PubMed1983

Absorption spectra of cytochrome P450CAM in the reaction with peroxy acids.

The reaction of Fe(III) cytochrome P450CAM with m-chloroperbenzoic acid was studied by rapid scanning absorption spectroscopy. Native low-spin enzyme produced spectra characteristic of two reaction phases that were marked by time intervals with isosbestic positions. The high-spin enzyme substrate complex yielded a series of Soret-region spectra whose properties were dependent on peracid concentration. The simplest model describing the results was a sequence of at least two spectral intermediates, that were not entirely homologous with data measured in reactions with microsomal P450LM2. Comparisons with related heme protein states indicate higher Fe(IV) oxidation levels provide a plausible interpretation of the P450CAM spectra.

Acetates↗
PubMed1983

Effects of SKF-10047 in the phencyclidine-dependent rat: evidence for common receptor mechanisms.

The repeated administration of phencyclidine (PCP, 72 mg/kg/day) to rats led to physical dependence, as evidenced by a withdrawal syndrome exhibited approx. 24-48 h following suspension of drug. All components of the withdrawal syndrome were suppressed by s.c. injections of PCP (16 mg/kg), (+/-)-N-allylnormetazocine (SKF-10047, 16 mg/kg) and (+)-SKF-10047 (16 mg/kg), but not by injections of saline or (-)-SKF-10047. Moreover, tolerance to the behavioral effects of PCP, as well as cross-tolerance to (+/-)-SKF-10047 and (+)-SKF-10047 were observed. These data indicate that PCP and the sigma opiate SKF-10047 share mechanisms of action, which are mediated by the (+)-isomer of the sigma agonist.

Animals↗
PubMed1982

Preliminary crystallographic data on cytochrome P-450CAM.

The cytochrome P-450CAM monooxygenase from Pseudomonas putida has been crystallized in three forms designated orthorhombic I, tetragonal I, and orthorhombic II. Conditions and parameters of crystal growth are presented along with the preliminary x-ray diffraction data including heavy atom derivatives.

Cytochrome P-450 Enzyme System↗