"Contact voltage" in nanoparticle/molecule connections.

This work presents conclusive evidence that connecting Pt and Co nanoparticles stabilized by an aluminum-organic shell with molecular spacers interacting with this shell can induce notable changes in the electronic structure of the metal. X-ray absorption spectroscopy measurements at the Al K-, the Pt L(III)-, and the Co K-edge provide consistent evidence for this effect. The changes induced by cross-linking with an acidic spacer are discussed in detail as an example to elucidate the mechanism of this effect. It turns out that a reconfiguration of the protection shell that occurs upon networking is responsible for the observed changes.

Thermal decomposition of (NH4)2[PdCl6] studied by in situ X-ray absorption spectroscopy.

In situ X-ray absorption near edge structure (XANES) investigations were carried out at chlorine K edge and palladium L3 edge to study the mechanism of the thermal decomposition of ammonium hexachloropalladate. The spectra show a characteristic feature for the initial step that might be explained as the formation of the precursor via ligand exchange (Cl --> NH3). Multiple scattering calculations (Feff 8) for the Cl K, Pd and Rh L3 edges were successful in simulating the XANES spectra of the precursor as well as the reference compounds (NH4)2 [PdCl4] and (NH4)3[RhCl6].

In situ analysis of sulfur in the sulfur globules of phototrophic sulfur bacteria by X-ray absorption near edge spectroscopy.

During the oxidation of sulfide and thiosulfate purple and green sulfur bacteria accumulate globules of 'elemental' sulfur. Although essential for a thorough understanding of sulfur metabolism in these organisms, the exact chemical nature of the stored sulfur is still unclear. We applied sulfur K-edge X-ray absorption near edge spectroscopy (XANES) to probe the forms of sulfur in intact cells. Comparing XANES spectra of Allochromatium vinosum, Thiocapsa roseopersicina, Marichromatium purpuratum, Halorhodospira halophila and Chlorobium vibrioforme grown photolithoautotrophically on sulfide with reference probes (fingerprint method), we found sulfur chains with the structure R-S(n)-R. Evidence for the presence of sulfur rings, polythionates and anionic polysulfides in the sulfur globules of these bacteria was not obtained.

Atropine and/or diazepam therapy protects against soman-induced neural and cardiac pathology.

Toxic doses of the organophosphonate anticholinesterase agent soman can produce neural and cardiac lesions in animals that survive the acute poisoning. The ability of two standard antidote drugs, atropine and diazepam, along with the oxime pralidoxime (2-PAM) Cl, were evaluated for their ability to block these pathological effects. Rats were challenged with a fixed dose (85 micrograms/kg, sc) of soman and treated im 5 min later with 25 mg/kg 2-PAM Cl and one of the following combinations of atropine (0.0, 1.0, 3.2, 10.0, or 32.0 mg/kg) and diazepam (0.0, 0.1, 0.32, 1.0, or 3.2 mg/kg) in a balanced design. The severity of acute anticholinesterase intoxication signs was rated 1 hr after exposure; Body weights and behavioral reactivity ratings were obtained daily for 16 days after exposure; brains and hearts of all surviving subjects were then evaluated for pathological changes. Soman challenge resulted in 33% lethality in animals that received only 2-PAM therapy; both atropine and diazepam reduced lethality in a dose-dependent fashion. Across all treatment conditions greater than 50% of the deaths occurred later than 24 hr after intoxication and treatment. Acute intoxication signs were differentially moderated by the two drugs: atropine reduced all six signs in a dose-dependent fashion; diazepam had no effect on lacrimation and eye bulb protrusion, antagonized signs of salivation and motor abnormalities in a dose-dependent manner, and antagonized the effects of soman on signs of physical activity and coordination only at low doses. All doses of diazepam and the highest dose of atropine moderated body weight loss and a syndrome of behavioral hyperreactivity observed after exposure. Brain pathology was significantly reduced by all doses of diazepam and/or the highest dose of atropine, but no single drug or drug combination was effective in protecting all animals in a group from some brain pathology. Both drugs blocked the development of cardiac lesions in a dose-dependent fashion. The results demonstrate that diazepam or high doses of atropine can antagonize the development of brain lesions that result from soman exposure. Pharmacological management of epileptiform motor abnormalities during the acute intoxication is critical for this effect. In contrast, soman-induced cardiac pathology may occur secondarily as a consequence of the severe brain lesions or develop independently of brain lesion formation due possibly to sympathetic overstimulation.

Effect of soman exposure on the acquisition of an operant alternation task.

Following recovery from soman administration, rats were trained on an operant alternation task with a time-out between response periods. As animals became proficient at the task, both the operant requirements and the length of time-out periods were gradually raised to Fixed Ratio 20 with a 20-second Intertrial Interval. Training sessions continued until animals attained criterion or 100 training sessions had been given. Soman produced a dose-related lethality and signs of cholinergic hyperstimulation. Although all saline controls and 90% of animals receiving 75 micrograms/kg soman attained terminal performance, only one-third of the animals given either 85 or 95 micrograms/kg soman were able to learn this task. Sessions to attain criterion performance produced similar dose-dependent results: All saline animals attained criterion, while only 60%, 33% and 33% of the animals given 75, 85 or 95 micrograms/kg soman respectively reached criterion. Additionally, both 85 and 95 micrograms/kg soman produced severe neural lesions, including cortical atrophy and ventricular dilation.

Long-term behavioral changes in rats following organophosphonate exposure.

The organophosphorus compound soman irreversibly inhibits cholinesterase in both the central and peripheral nervous systems. High doses of this compound produce seizures and death in animals. Surviving animals exhibit neural lesions and behavioral abnormalities. The behavioral effects of a single exposure to soman were evaluated in rats injected with 50 micrograms/kg or 85 micrograms/kg soman or with saline. Each rat was tested for either activity in an open field or performance in a 14 choice point multiple T-maze. All rats were then tested for reactivity to tactile stimuli. Some rats exposed to soman showed increased activity in the open field, learning deficits in the Stone maze, and increased reactivity to tactile stimuli, while others showed behavior similar to that of controls. An increase in reactivity was correlated with increased open field activity and with poor performance in the Stone maze. Rats which had received soman and were abnormal in behavioral tests were more likely to have abnormal brain pathology than rats which had received soman and were normal in behavioral tests.

Change in atropine dose effect curve after subacute soman administration.

Thirty-one adult male rats were trained on a two component (FR10-extinction) operant task. After establishment of an atropine sulfate dose effect curve (vehicle, 1.0, 1.8, 3.2, 5.6 or 10.0 mg/kg), all rats were injected SC with 35.0 micrograms/kg soman three times per week for four weeks. One, twenty-eight and fifty-six days after the last soman injection, additional atropine tests were given. Atropine produced significant dose related decreases in FR10 responding at 3.2, 5.6 and 10.0 mg/kg during the initial dose effect curve with no effect on extinction responding. Although four rats died during the soman exposure period, the remaining rats exhibited neither signs of organophosphate toxicity nor significant disruptions in FR responding. However, a significant increase in extinction component responding was seen on soman injection days. The atropine dose effect curve for FR10 responding showed a significant shift to the left on the day after the last dose of soman. However, the dose effect curves at 4 and 8 weeks were the same as the initial curve. These results provide behavioral evidence that chronic soman exposure results in a supersensitivity to the antimuscarinic drug, atropine, possibly due to a down-regulation in the number of muscarinic receptors.

Drug discrimination and cross generalization between two methylxanthines.

Twenty-one rats were trained to discriminate 32 mg/kg caffeine from saline in a two-lever drug discrimination task (variable ratio) while another ten rats were trained to discriminate 56 mg/kg theophylline from saline. For each group, dose-effect curves (% drug-lever responses and overall response rate) were obtained for both caffeine and theophylline. Significant dose-related generalization of each training drug was found for both the caffeine- and theophylline-trained rats. Concomitant dose-related decreases in overall response rate also were apparent. Similar dose-related effects were seen with cross-generalization tests for various doses of the other xanthine. The nature of the training session preceding the test session was found to have an effect on discrimination performance at intermediate test doses. Drug appropriate responding was higher and overall response rate was lower after saline- than after drug-training days. Such data may suggest the possibility of short-term tolerance to caffeine's cue. That the discriminative cue was specific to the xanthines was shown by the lack of generalization seen after either amphetamine or metrazol.

Methylxanthine discrimination in the rat: possible benzodiazepine and adenosine mechanisms.

Rats were trained to discriminate either caffeine or theophylline from saline using a two-lever discrimination paradigm. Since methylxanthines have been found to interfere with agonist binding at both adenosine and benzodiazepine (BDZ) receptors, chlordiazepoxide (CDP) and L-PIA (an adenosine analog) were tested for generalization to and blockade of both xanthine cues. Neither L-PIA nor CDP generalized to either xanthine cue, although both produced dose-related decreases in response rate. CDP, but not L-PIA, produced dose-related decreases in drug-lever responses when combined with training doses of caffeine or theophylline. Response rates indicated a complex interaction between the xanthines and both L-PIA and CDP. When combined with the caffeine training dose, pentobarbital also produced a dose-dependent decrease in response rate but not in drug lever choices. Finally, papaverine generalized to the caffeine cue in a dose-dependent fashion. In a second experiment, rats trained to discriminate CDP from saline showed no generalization in L-PIA tests. CDP-appropriate responding was not significantly affected when the CDP training dose was combined with caffeine. These data indicate that: (a) methylxanthine interactions with L-PIA and CDP on response rate likely involve blockade of adenosine mechanisms; (b) the xanthine cue does not appear to depend on interactions with adenosine receptors; and (c) the xanthine cue may involve effects on cyclic AMP activity and/or interaction with the BDZ/GABA receptor complex.

Discriminative stimulus properties of methylxanthines and their metabolites in rats.

Rats were trained to discriminate methylxanthines from saline under a two-lever concurrent variable ratio schedule of reinforcement. One group was trained to discriminate between saline and 32 mg/kg caffeine. A second group was trained to discriminate between 56 mg/kg theophylline and saline. Rats reliably discriminated between saline and the training methylxanthine, displaying graded generalization curves across training-drug doses. Caffeine-trained rats demonstrated caffeine-appropriate responding when tested with theophylline, paraxanthine, and 3-methylxanthine. Theobromine failed to generalize to the caffeine cue at test doses up to 75 g/kg. In contrast to the caffeine group, rats trained to discriminate theophylline from saline were less sensitive (higher ED50) to the effects of caffeine and paraxanthine test doses. Only partial generalization to the theophylline cue occurred at paraxanthine doses up to 100 mg/kg. Based upon these data, it is suggested that the underlying substrate(s) for the caffeine cue is in some respects different from the substrate(s) for the theophylline cue.

Transfer of a learning set between drug states in monkeys.

Four adult male rhesus monkeys, while in either a pentobarbital-induced drug state or a saline control state, were trained on a series of 12 oddity problems. Tests in the opposite drug or saline state were administered after acquisition of each problem in order to determine the amount of transfer between the disparate states. All tests included presentation of problems not previously seen (novel problems). Tests 2-11 also included presentation of problems trained beyond criterion level (overtrained problems). During early tests only the overtrained problems exhibited transfer to the opposite drug or saline state. However, during the later tests, as the monkeys acquired the learning set in the training state, both the novel and overtrained problems were correctly solved in the test state. This indicates that the concept of oddity, rather than solution of specific problems, transferred between drug states. Interestingly, the overtrained problems exhibited greater transfer on the later tests than on early tests. This may suggest that the transfer due to overtraining is not the same as the transfer due to acquisition of the oddity learning set.

Relationship between caffeine discrimination and caffeine plasma levels.

Rats, trained to discriminate 32 mg/kg caffeine from saline in a two-lever operant task, were tested for the presence of caffeine-appropriate lever responding at various intervals after the intraperitoneal injection of 32 mg/kg caffeine. Following completion of all behavioral tests, caffeine plasma levels were determined in the same animals at the same intervals after caffeine administration. After injection, both caffeine levels and caffeine-appropriate responding showed rapid increases followed by a differential decline.

Caffeine discrimination in the rat.

Rats were trained to discriminate 32 mg/kg caffeine from saline in a two-lever appetitive task. Across a range of caffeine test doses (1-32 mg/kg) rats showed a dose related generalization to the training cue. At intermediate caffeine dose levels, caffeine appeared to produce a more potent cue on tests following saline-training days than after drug-training days. Several psychomotor stimulants (d-amphetamine, methylphenidate, nicotine and TRH) failed to generalize to the caffeine cue. In contrast, theophylline did generalize to caffeine at a dose roughly twice that of the caffeine training dose.