Subtle Behavioral Changes Research Articles

Hypofluorous acid and acetonitrile: the taming of a reagent

The strong oxidant produced by the reaction of elemental fluorine with acetonitrile containing ca. 10% water has been shown to be hypofluorous acid, HOF, which is stabilized by complexing to the solvent. The reaction represents a new and convenient method of preparing and handling HOF, a unique oxygenating reagent. The presence of acetonitrile results in subtle but significant changes in the chemical behavior of the HOF. Vibrational and NMR spectroscopic studies of the solutions resulting from this reaction, as well as of solutions prepared by dissolving neat HOF in dry acetonitrile, have shown that the complex is a 1:1 hydrogen-bridged entity, in which the HOF proton is most likely bonded to the nitrogen atom of the nitrile. The 19F NMR data indicate that the complexation reaction has an equilibrium constant of ca. 3 at room temperature, and that the enthalpy of formation of the complex is −14.3 ± 0.5 kJ mol −1. The success of this method of synthesizing hypofluorous acid is a consequence of the very slow reaction between HOF and low concentrations of water in acetonitrile. This reaction accelerates drastically as the water content increases. As the solution composition approaches 100% water, the rate constant appears to approach a limit of about 0.7 s −1 at 25 °C, which may be the actual rate of reaction of HOF with the water.

Chronic exposure to low doses of MPTP. II. Neurochemical and pathological consequences in cognitively-impaired, motor asymptomatic monkeys

Chronic low-dose MPTP exposure was previously found to impair cognitive performance in monkeys. These monkeys developed deficits in performance of delayed response and delayed alternation tasks but maintained performance on visual pattern discrimination. This, along with other subtle behavioral changes, occured in the absence of gross parkinsonian motor symptoms. The present study reports the results of neurochemical and neuropathological examination of the brains of these animals. Chronic low-dose MPTP exposure resulted in profound decreases in caudate dopamine (DA) levels and slightly less severe depletions in the putamen. Increases in striatal HVA/DA ratios suggest an increase in DA turnover in these areas. In contrast to striatal DA depletions, we found significant increases in striatal serotonin levels without an associated increase in serotonin turnover. At the cortical level, we found inconsistent changes in frontal cortical DA levels and variable decreases in norepinephrine levels. Since the most profound and consistent deficits were in the nigrostriatal dopamine system. We also suggest that the most of the behavioral consequences of chronic low-dose MPTP exposure stem from the striatal dopamine depletion. We also suggest that the maintenance of motor function in the presence of massive striatal DA depletions may be due to less impairment of putamen DA vs. caudate DA, by an increase in striatal DA turnover, a compensatory increase in serotonin availability, or a combination of these and possibly other as yet undetermined compensatory mechanisms. Furthermore, we propose the present model utilizing chronic low-dose exposure to MPTP as a model for the early, compensated form of Parkinson's disease.

A ‘silent’ intracranial complication of frontal sinusitis

Intracranial complications of frontal sinusitis, although rare today, do still develop despite widespread use of antibiotics. We report a case which demonstrates how silently a frontal lobe abscess may present with subtle changes in mood and behaviour, with no focal neurological signs. Diagnosis and management are discussed and a brief review of the incidence of intracranial complications of frontal sinusitis, mode of spread, clinical presentation, investigations, treatment and bacteriology is presented.

Solvent swelling influences the electrochemical behavior and stability of thin films of nitrated poly (styrene)

The electrochemical behavior and stability of thin films of poly(nitrostyrene) (PNS) and a partially dinitrated derivative of PNS (PDNS) have been examined in acetonitrile. Qualitative information regarding the extent of solvent swelling of these polyelectrolyte films in non-aqueous solvents is obtained using the electrochemical quartz crystal microbalance (EQCM) technique, both by measuring the frequency changes due to solvent swelling and by measuring the conductance (impedance) spectra of the quartz crystal/polymer film composite resonator in the different oxidation states. Extensive solvent swelling as a function of the number of reductive scans is correlated with instability of the films toward dissolution or delamination and with subtle changes in electrochemical behavior. The effectiveness of thermal pretreatments (which presumably induce crosslinks of some type) for enhancing film stability by slowing the rate of swelling is examined. For certain types of films, it is shown that the transport processes which serve to achieve electroneutrality at high scan rates may occur on a different time scale (i.e. faster) than those which serve to attain thermodynamic equilibrium. The implication is that transient, non-equilibrium states may be prepared during switching whose composition is not necessarily that dictated by the equilibrium state, and that manipulation of these transient states to achieve faster switching rates may be done independently of equilibrium considerations, at least in some cases.

SWIMMING BEHAVIOR AS AN INDICATOR OF SUBLETHAL TOXICITY IN FISH

Swimming behavior of fish is impaired by exposure to a diversity of contaminants. Gross aberrations in swimming can be qualitatively assessed while subtle changes in swimming behavior arising from sublethal exposures can be detected through a more detailed analysis of this response. Compared to other swimming behavior variables, the physical capacity to swim against water flow tends to be affected at relatively high toxicant concentrations and often presages mortality. Orientation to water flow, however, is altered at sublethal concentrations. Frequency of activity is a more sensitive measure in detecting contamination than measurements of survival alone. Alterations in swimming behavior have been detected during exposures to various contaminants at concentrations as low as 0.7 to 5% of their LC50 values and at concentrations that subsequently inhibited growth after longer periods of exposure. Analysis of swimming patterns provides even higher resolution for analysis of swimming behavior, and increased availability of the instrumentation necessary for such measurements should facilitate use of this approach. Fish swimming activity can easily be incorporated in test protocols to expand the sensitivity of standard toxicity tests.

Swimming behavior as an indicator of sublethal toxicity in fish

AbstractSwimming behavior of fish is impaired by exposure to a diversity of contaminants. Gross aberrations in swimming can be qualitatively assessed while subtle changes in swimming behavior arising from sublethal exposures can be detected through a more detailed analysis of this response. Compared to other swimming behavior variables, the physical capacity to swim against water flow tends to be affected at relatively high toxicant concentrations and often presages mortality. Orientation to water flow, however, is altered at sublethal concentrations. Frequency of activity is a more sensitive measure in detecting contamination than measurements of survival alone. Alterations in swimming behavior have been detected during exposures to various contaminants at concentrations as low as 0.7 to 5% of their LC50 values and at concentrations that subsequently inhibited growth after longer periods of exposure. Analysis of swimming patterns provides even higher resolution for analysis of swimming behavior, and increased availability of the instrumentation necessary for such measurements should facilitate use of this approach. Fish swimming activity can easily be incorporated in test protocols to expand the sensitivity of standard toxicity tests.

Whole life history studies of coho salmon ( Oncorhynchus kisutch) following embryonic exposure to benzo[ a]pyrene

Previously we observed that a single embryonic exposure of salmonid embryos to benzo[ a]pyrene was capable of inducing subtle behavioral changes following hatching. This study determines whether coho salmon which had survived an identical benzo[ a]pyrene exposure were capable of successfully competing with their normal counterparts under natural conditions. Initially, we examined the uptake and retention of benzo[ a]pyrene as well as the ability of this compound to compromise normal metabolic activity. Subsequently, hatchery reared coho salmon, which return to their site of birth when sexually mature, were exposed to benzo[ a]pyrene at one of two stages of embryonic development. These fish, as well as appropriate controls, were individually tagged prior to release for seaward migration. As fish returned from sea, length, weight, sex, and pathology were compared among the groups.

Signs and symptoms associated with malignancy-induced hypercalcemia

Hypercalcemia is a common life-threatening complication that often produces discomfort for the oncology patient. Prompt detection of this complication is imperative to prevent death and reverse uncomfortable symptoms. Laboratory analysis of a serum blood sample is presently the only means available to quantify hypercalcemia. A descriptive study was undertaken to determine what symptoms prompt oncology patients and their families to seek treatment of the hypercalcemia and to identify symptoms commonly associated with mild, moderate, and severe hypercalcemia. Seven hypercalcemic oncology patients were interviewed and observed on admission and during hospitalization for treatment of hypercalcemia. An identified significant other was also interviewed on admission and throughout the hospitalization to provide the researcher with information about subtle behavioral changes. A check-list of symptoms identified in the literature as being associated with hypercalcemia was completed. Symptoms that commonly led to admission included constipation, confusion, weakness, and anorexia. The most evident changes in a particular symptom within a given degree of hypercalcemia occurred in the mental status symptoms. The resulting data have implications for nurses in terms of patient assessment and of teaching patient and family about signs and symptoms of hypercalcemia that are observable at home.

Subtle behavioural changes produced in rat pups by in utero exposure to haloperidol

Prenatal exposure to a dopamine receptor blocking agent such as haloperidol (given to the mother at a dose of 0.5 mg/kg s.c. from day 4 to day 15 of gestation) produced subtle behavioural changes in rat pups. Haloperidol decreased the rate of ultrasonic vocalization in 4-day-old male pups removed from the nest. The changes in ultrasonic emission elicited by in utero exposure to this neuroleptic were markedly different from those produced by its administration during the early postnatal period. Moreover, adult male rats treated prenatally with haloperidol exhibited a significant increase in the intensity of ultrasonic 22 kHZ post-ejaculatory calls emitted during sexual behaviour. The duration of the period of the 22 kHz calls emission was also significantly increased by haloperidol treatment. These results confirm that ultrasonic vocalization in rats is a sensitive indicator of subtle changes in adverse treatments administered during development.

Behavioral teratology: an inappropriate term for some uninterpretable effects

Since the thalidomide tragedy, the testing of new drugs on pregnant experimental animals has become a requirement in all countries. Many countries have recently introduced tests for subtle behavioral changes (in the absence of morphological damage). However Flaminio Cattabeni and Maria Pia Abbracchio argue that we do not yet know enough about the significance of these changes to make valid interpretations, or to extrapolate from animals to humans. They also propose that the term ‘behavioral teratology’ with its negative implications should be replaced by the more appropriate term ‘chemical imprinting’ to account also for chemicals inducing behavioral effects in animals which do not necessarily cause true neurological damage.

Direct measurement by neutron diffraction of the solvation of polar and apolar molecules. The hydration of the tetramethylammonium ion

Using the isotope-substitution neutron diffraction first difference method, we have studied the cation hydration in three concentrations of tetramethyl-ammonium chloride in D2O. At low (0.50 mol kg–1) concentration, the results are consistent with a defective and disordered cage model, as would perhaps be expected for higher tetra-alkylammonium ions. As concentration is increased to 1.00 mol kg–1, where measurements in an H2O/D2O mixture give information on water orientations, there appears to be a qualitative change: the behaviour of the TMA appears to be more like that of a strong cation. Chloride substitution confirms that the anion hydration is normal, and we explain this intermediate concentration behaviour in terms of the effects of the anion rather than the TMA. At high concentrations a further change occurs and the hydration structure seems to return to a defective and disordered cage, presumably with the anion incorporated into it. These results appear to indicate subtle changes in hydration behaviour which are thought to be of chemical and biological importance.

Psychologic and Behavioral Effects of Antiepileptic Drugs in Children: A Double-Blind Comparison Between Phenobarbital and Valproic Acid

Traditional clinical monitoring of children with epilepsy does not appear to be sufficiently sensitive to cognitive functioning and behavioral problems. Although subtle, these changes may alter a child's ability to perform well in school and in society. Physicians must prevent seizures without producing intolerable side effects, and ways of more appropriately assessing these side effects must be developed. In this double-blind, counter-balanced, crossover study of 21 children, the effects of phenobarbital and valproic acid on cognitive functioning and behavior were measured. There was no difference in seizure control between the drugs, and each medication was maintained in the therapeutic range for 6 months (mean phenobarbital level, 21.2 micrograms/mL; mean valproic acid level, 94.1 micrograms/mL). Children were treated with each drug for 6 months. Differences between the drugs were seen on measurements of cognitive function and behavior. On four tests of neuropsychologic function, children performed significantly less well while receiving phenobarbital (P less than .01). There was no evidence that the patients were sedated or less able to perform continuous performance tasks while receiving phenobarbital. Parental assessment of behavior indicated significantly worse behavior with the phenobarbital regimen for three items (P less than .01) and children were measurably more "hyperactive" (P less than .05). Routine clinical assessment of the patients did not reveal differences between the drugs with respect to routine laboratory measurements or side effects as assessed by history or physical examination. Although children may appear to tolerate a medication without clinically apparent problems, subtle but significant changes in intellectual function and behavior may be occurring. Additional, more sensitive, methods of monitoring patients while receiving these drugs is necessary.

Behavioural changes in rats after prenatal administration of typical and atypical antidepressants.

Prenatal administration of typical (desipramine, DMI) and atypical (viloxazine, VX and mianserin, MS) antidepressants, at dose levels which do not influence reproductive success or neonatal mortality, produces subtle behavioural changes in offspring of treated rats. Physical signs, such as pinna detachment (unfolding of external ear) and eye opening, were not modified by prenatal exposure to any of the antidepressants tested. However, at 23 days of age, DMI, MS and VX (only in males) pretreated rats showed higher levels of locomotor activity with respect to the control group. At 60 days of age, locomotor activity levels in DMI-exposed animals were still higher than in the saline-pretreated rats.

Comparison of the behavioural and acute toxicity of copper to sheepshead, Atlantic croaker and pinfish

Sheepshead ( Archosargus probatocephalus), Atlantic croaker ( Micropogon undulatus) and pinfish ( Lagodon rhomboides) were each exposed to aqueous solutions of reagent grade cupric chloride in artificial seawater in four static bioassays. The 24, 48, 72 and 96-h TL m were determined to be, respectively, 4.17, 3.02, 2.19 and 1.14 mg Cu 2+·I −1 for sheepshead, 9.15, 7.55, 7.20 and 5.66 mg Cu 2+·I −1 for croaker, and 7.33, 4.43, 4.14 and 2.75 mg Cu 2+·I −1 for pinfish. These results are compared with literature values of experimental concentrations of copper producing subtle behavioural changes in these species.

Acute toxicity of copper to sea catfish

Sea catfish ( Arius felis) were exposed to aqueous solutions of reagent grade cupric chloride in artificial seawater ( 30.0±2.0‰, 21–23°C) in four static bioassays. The 24, 48, 72 and 96 h LC 50 were calculated and found to be 5.43, 4.17, 3.57 and 2.40 mg l. −1 copper, respectively. Experimental concentrations of copper producing subtle behavioral changes in this species correspond to less than 0.3% of the 72 h LC 50. Based on this comparison with literature values, a new, maximum ‘safe’ concentration for copper in marine waters of 0.01 mg l. −1 is proposed.

Psychotropic Drugs in Pregnancy and Lactation

Accurate prediction of fetal/neonatal risks following maternal psychotropic drug consumption by the human will require much additional study. Based upon our present understanding of fetal exposure to psychotropic drugs, there would appear to be an increased risk for spontaneous malformations in the case of lithium. There have been inconsistent reports of structural abnormalities following exposure to phenothiazines and benzodiazepines. In animal models that demonstrate structural changes due to neuroleptic exposure, in general, extremely large dosages of medication had been given. Thus, their correlative value is limited. Behavioral alterations in animals following drug exposure during pregnancy tend to support increased concerns about the safety of psychotropic drugs for the fetus but cannot be used alone in making a final decision. Behavioral studies evaluating drugs in breast milk have been restricted to experimental animals; hence, the associated risks from this form of drug dosing in man remain unknown. At present, neither gross anatomic nor motor side effects have been apparent in the infant. The question of the development of subtle behavioral changes as a long-term consequence will remain undetermined until careful assessments have been completed.

Responses of bowhead whales (Balaena mysticetus) to activities related to offshore oil and gas exploration

The presence and behavior of bowhead whales near offshore oil and gas exploration activities in the eastern Beaufort Sea were studied during August 1980. Numerous bowheads were within 5 km of an artificial island construction site where a large dredge, a barge camp, and several boats were operating. In a different situation, the physical presence of a 16.1-m boat had no apparent effect on the behavior of bowheads at a distance of 3.7 km. Subtle changes in behavior were noted when the vessel's engines were idling with propellers disengaged. Bowheads within 1 km of vessels responded by spending briefer periods at the surface, by respiring fewer times per surfacing, and by moving away from the disturbance. Surfacing and breathing patterns returned to normal following the disturbance, while interanimal distances remained greater. Whales 13 km from an underwater seismic exploration operation did not behave differently from animals in the same area on days preceding and following the seismic work. Additional data from 1981 will also be presented. (See a companion paper on underwater noise near the above industry activities by C. R. Greene, Abstract MMI0, this session.) [Work supported by the Bureau Land Management.]

Detailed kinetic analysis of Shay chloroleukaemia cell population propagated in permanent suspension culture in vitro.

Detailed kinetic analysis of a growing cell population is difficult, even when assay conditions are nearly ideal. Therefore, it is usually essential to perform several types of experiments and analyse all the results in terms of a mathematical model, the use of which is not limited a priori by a specified application. In the present study we investigated cell population kinetics using rat chloroleukaemia cells propagated in suspension culture in vitro. The parameters were measured: doubling time of the population, fraction of labelled mitoses, changes in labelling index with time after pulse labelling, continuous labelling and stathmokinetic index. Analysis of the results was based on a computer program CECAM, which is a stochastic model capable of simulating essentially all types of kinetic experiments based on presently known assay techniques. The results showed that precise and reliable information on cell population kinetics could not be obtained from the analysis of any single type of experimental data. In particular, the technique of labelled mitoses underestimated the duration of the G1 phase, owing to subtle label-induced changes in population behaviour. These changes could not have been detected with any certainty without rigorous quantitative comparisons with other types of experimental data. As a whole, however, results obtained by the different techniques were in agreement and the kinetic behaviour of chloroleukaemia cells in vitro could be established in detail. In certain circumstances even minute changes in the kinetic parameters of the cells can modify population behaviour drastically. To study these cases adequately the experiments must be designed with utmost care, preferably with the aid of preceding simulations. This is because demonstration of small primary changes in population kinetics may be beyond the limit of detection of any single assay method.

Effects of caudate or frontal cortex ablations in cats and kittens: Passive avoidance

A simple step-down passive avoidance task was used to evaluate the perceptual awareness of a fearful situation in 15 normal cats and in animals with extensive lesions of the caudate nuclei or the frontal cortices. The lesions were made both in kittens and in adults but all animals were tested as adults. On each of 2 days the animal was twice placed on a platform and the latency to step-down was measured. After trial 2 of day 2 the animal received a 10-s unescapable shock. Single step-down retention trials were carried out at 24- and 48-h and 1-week after the one-trial training. There was a significant conditioning effect for all groups. There were significant group differences only on trial 1 of day 1 where the adult acaudates stepped down significantly slower than both the intact cats and the kitten-operated acaudates and on the 1-week retention-extinction trial where the same animals stepped down faster than the other groups. For the adult acaudates there was a significant inverse correlation between lesion size and the step-down latency for both trials of the 1st preshock day and for the trial immediately preceding shock. For the kitten acaudates no significant relationships were found between any of the parameters and the lesion magnitude. These data show that (i) animals with total removal of the caudate nucleus or the frontal cortex learned one-trial passive avoidance as readily as sham-operated and intact cats; (ii) adult acaudate cats were distinguishable from the other groups only by slower step-downs on the first habituation trial prior to shock, and more rapid extinction than either kitten acaudates or other control animals. We conclude that animals with extensive lesions of the caudate nuclei or frontal cortices are capable of avoiding an electric footshock. There are subtle changes in that avoidance behavior which may be attributed to the peculiarities in reactivity and activity previously described in acaudate animals.

Naloxone Reversal of Mild Neurobehavioral Depression in Normal Newborn Infants after Routine Obstetric Analgesia

To investigate the presence of subtle narcotic depression following maternal narcotic analgesia, we have evaluated the effects of naloxone versus placebo in a double-blind parallel group study in 43 normal term newborn infants whose mothers had received routine narcotic analgesia within six hours prior to delivery. Infants were given either an intramuscular injection of 20 μg/kg naloxone or 0.20 ml/kg placebo after determination of the one-minute Apgar score, and the following measurements were compared: Apgar scores at one and five minutes, capillary blood gas values at one, 60, 120, and 240 minutes, and neurobehavioral assessments at one, 4, and 24 hours. No adverse effects from naloxone were observed. Neither Apgar scores nor capillary blood gas determinations differed significantly between the two groups. Response to sound was significantly higher in the naloxone group at 24 hours. The alertness score was significantly higher for the naloxone group at one and four hours; the general assessment score for the naloxone group was significantly higher at four and 24 hours. Average scores of naloxone and placebo groups were also different at four and 24 hours of age. These data demonstrate that maternal narcotic analgesia may produce subtle changes in alertness and general behavior not reflected by Apgar scores or respiratory status, potentially reversible by administration of naloxone shortly following delivery.