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Biomedical subjects

S E Robinson

Publications and source records attributed to S E Robinson.

At least 19 recordsLinked to original sources

Extracellular aspartate concentration increases in nucleus accumbens after cocaine sensitization.

Rats were sensitized to cocaine (15 mg/kg, i.p.) by 6 daily injections followed by a 48 h withdrawal prior to cocaine challenge. Involvement of excitatory amino acids in behavioral sensitization was assessed by comparing extracellular levels of aspartate and glutamate in the core of the nucleus accumbens in response to the first cocaine injection and the final cocaine challenge. Intracerebral microdialysis of the nucleus accumbens in freely moving awake rats allowed the comparison of behavioral state with extracellular aspartate and glutamate concentrations. Increased nucleus accumbens extracellular concentration of aspartate, but not glutamate, was observed in rats exhibiting behavioral sensitization to cocaine.

Animals

Recruitment and retention of psychosocial rehabilitation workers.

Recruitment and retention of direct service workers can be a major problem for administrators of community mental health organizations. This paper, based on a nationwide study of psychosocial rehabilitation workers and administrators, examines the congruity of worker and administrator perceptions of worker motivation for entering and leaving the field. Workers are motivated by the intrinsic nature of the work to enter into and stay in the field. Job burnout is as important as low pay in forcing workers out of the field. Administrators, however, perceive money to be a major factor motivating workers to enter the field and perceive external opportunities as forces that pull them away. Thus, administrators must address their workers' needs if their agencies are to offer quality services.

Adult

Turnover intentions of community mental health workers in psychosocial rehabilitation services.

Staff turnover is an important topic for community mental health administrators. This paper reports on turnover intentions of PSR workers, a rapidly growing sector of the community mental health labor force as reported in a nationwide survey. A predictive model of intended turnover, suggested by literature in the field as well as study finding, included worker characteristics, job characteristics and worker attitudes. It was found that seven variables predicted intended turnover: younger age, higher emotional exhaustion, a feeling of lower job fulfillment, the lack of a perception of a career path, having a master's degree, having held a previous job in PSR and working with clients who have both a mental illness and AIDS. To assist agencies in reducing turnover, organizational policies and recommendations for staff development are discussed.

Adult

Postnatal methadone exposure doe not prevent prenatal methadone-induced changes in striatal cholinergic neurons.

On postnatal day 4, rats exposed to methadone prenatally but fostered to control dams, as well as those fostered to dams treated with methadone, exhibited significant reductions in striatal acetylcholine (ACh) content. This suggests that neonatal withdrawal from methadone is not responsible for the effects of prenatal exposure on cholinergic development in the early perinatal period. The effects of perinatal exposure to methadone on serotonin (5HT) and dopamine (DA) metabolism do not appear to be strictly related to changes in ACh content. Although prenatal exposure reduces 5-hydroxyindole acetic acid (5HIAA) content, changes in 5HT content prevent significant changes in the ratio 5HIAA/5HT. Pups exposed to methadone only prenatally (withdrawal group) exhibited a decreased DOPAC/DA ratio, whereas pups in the treatment group exposed to methadone both pre- and postnatally exhibited an increased DOPAC/DA ratio.

3,4-Dihydroxyphenylacetic Acid

Perinatal exposure to methadone affects central cholinergic activity in the weanling rat.

Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. Perinatal methadone exposure disrupted cholinergic activity on postnatal day 21 as measured by the turnover rate of acetylcholine (TRACh) in both female and male rats, although there were some sexually-dimorphic responses. The most profoundly affected brain region was the striatum, where prenatal exposure to methadone increased ACh turnover, whether or not the rats continued to be exposed to methadone postnatally. It appears unlikely that neonatal withdrawal contributes to brain regional changes in ACh turnover, as continued postnatal exposure to methadone did not prevent the prenatal methadone induced changes.

Acetylcholine

Gestational cocaine and ethanol exposure alter spontaneous and cocaine-induced behavior in weanling rats.

The developmental and behavioral effects of prenatal exposure to cocaine and/or ethanol were examined in rats. Pregnant rats received ethanol (E; 2 g/kg, b.i.d.) orally, cocaine (C; 6 mg/kg/day, IV), or both (C/E) on gestational days 8-20. Controls consisted of pair-fed (PF) and untreated (UNT) groups. Offspring were weighed and examined for developmental markers beginning postnatal day one (PD1). On PD21 pups were individually observed in an open-field following either an injection of cocaine (10 mg/kg, IP), an injection of saline, or no treatment. Drug-treated and PF dams ate less food and gained less weight than the UNT dams. C and E litters had slightly increased mortality rates. Pups from both the C and E groups appeared less sensitive to the locomotor stimulant effect of cocaine. Pups from the E group engaged in significantly less spontaneous stereotypic locomotion than UNT and PF pups, while male pups from the C group exhibited a decrease in spontaneous exploratory behavior. Thus, prenatal exposure to C or E altered spontaneous and/or cocaine-induced behavior in weanling-aged rats, while the C/E combination did not augment either effect.

Animals

Developmental consequences of intermittent and continuous prenatal exposure to 1,1,1-trichloroethane in mice.

The effects of 1,1,1-trichloroethane (TCE) on physical and behavioral development were examined in CD-1 mice prenatally exposed under two regimens. In the first study, pregnant mice were exposed to either 2,000 ppm TCE or filtered air for 17 hrs. during gestational days (GD) 12-17. A third group remained untreated. The results revealed no differences on pregnancy outcome. TCE-exposed pups gained less weight, exhibited delays in developmental landmarks and acquisition of the righting reflex, had poorer performance on tests of motor coordination and exhibited delays in negative geotaxis relative to sham or untreated pups. A second experiment was designed to more closely parallel the intermittent, acute, high-concentration pattern of solvent abuse. Pregnant mice were exposed for 60 min. to 8,000 ppm TCE or sham placement in exposure chambers three times/day during GD's 12-17. The results were very similar to what were obtained in the more continuous exposure study. TCE-exposed pups gained less weight, had delays in developmental landmarks and acquisition of the righting reflex and exhibited weaker grip strength, poorer negative geotaxis and less rooting intensity in comparison to sham pups. These data provide evidence for the behavioral and developmental teratogenicity of prenatal TCE exposure late in gestation.

Animals

Perinatal methadone exposure produces physical dependence and altered behavioral development in the rat.

Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that the following prenatal/postnatal exposure groups were obtained: water/water, methadone/water, water/methadone and methadone/methadone. Methadone slightly reduced litter size, particularly the number of male offspring, and reduced litter birth weight. The induction or maintenance of physical dependence in the postnatal methadone exposure groups was confirmed by an experiment in which PD19 pups were challenged with naloxone (1 mg/kg, s.c.). Methadone concentrations were assayed in pup brain on postnatal days 4, 10 and 22. Postnatal exposure to methadone via maternal milk produced measurable levels of methadone which decreased with age. Neuromuscular and physical development were assessed. Exposure to methadone accelerated acquisition of the righting reflex, but tended to delay the acquisition of the negative geotaxic response. Postnatal exposure to methadone was associated with decreased somatic growth as measured through postnatal day 21. The older pups (postnatal day 21) exposed to methadone exhibited variations in activity levels: pups exposed to methadone both prenatally and postnatally exhibited the least amount of spontaneous locomotor activity and pups exposed only postnatally exhibited the most activity. Therefore, it is possible to induce and/or maintain physical dependence via lactation in rat pups fostered to methadone-treated dams. Perinatal exposure to methadone by this route produces several subtle disruptions of pup development in the absence of gross maternal or fetal toxicity.

Analysis of Variance

The pharmacology of respiratory disorders related to anesthesia.

The pharmacology of disorders of the respiratory system focuses on one major parameter--bronchodilatation. Drugs are rated as effective purely on how well they reverse brochoconstriction. Patients' conditions are considered reversible if there is a 20% increase in flow rates after a bronchodilator is administered. This article evaluates many of the drugs used in the treatment of reactive airway diseases such as asthma. Particular emphasis is placed on the anesthetic drugs used during the perioperative period.

Anesthetics

Cocaine increases extraneuronal levels of aspartate and glutamate in the nucleus accumbens.

Intracerebral microdialysis was used to assess the effects of cocaine-HCl on extracellular concentrations of the excitatory amino acids aspartate and glutamate in the nucleus accumbens of awake, freely moving rats. After an initial equilibration period, cocaine (7.5, 15 or 30 mg/kg) or saline was injected i.p., and samples were collected for an additional 2 h. The highest dose of cocaine (30 mg/kg, i.p.) caused a 4-fold increase in glutamate levels and an 18-fold increase in aspartate levels over baseline. To verify that the source of the extracellular aspartate and glutamate was neuronal, additional experiments were conducted using Ca(2+)-free microdialysis buffer, and buffer containing 10 microM tetrodotoxin. Local perfusion with Ca(2+)-free buffer reduced the increase of extracellular aspartate and glutamate in rats injected with 30 mg/kg cocaine. Tetrodotoxin significantly decreased the cocaine-induced increase in excitatory amino acids, but not the behavioral response.

Analysis of Variance

Effects of cocaine and the cocaine analog CFT on glutamatergic neurons.

The effects of cocaine and the cocaine analog methyl-3-beta-(p-fluorophenyl)-1 alpha H, 5 alpha H-tropane-2b-carboxylate (CFT) on glutamate turnover rate were studied in the nucleus accumbens, striatum, frontal cortex, and parietal-cingulate cortex of the rat, using neurotransmitter turnover rate as an estimate of the activity of the glutamatergic neurons. Both cocaine [15 or 30 mg/kg, intraperitoneally (IP)] and CFT (2.2 mg/kg, IP) increased glutamate turnover in the nucleus accumbens, although the time course of their actions differed. These effects on glutamate turnover appeared at times after maximal motor activation of the animals had occurred. On the other hand, neither cocaine nor CFT affected glutamate turnover in the frontal cortex, parietal-cingulate cortex, or striatum. Neither cocaine nor CFT affected the content of glutamate or glucose in any brain region studied. Thus, although cocaine and CFT affect glutamatergic neurons in the CNS, these actions are not generalized across the CNS, but are restricted to a specific brain region.

Analysis of Variance

Effect of continuous-wave ultrasound on blood flow in skeletal muscle.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the effect of ultrasound on forearm, skin, and muscle blood flow. SUBJECTS: Twenty volunteers without known vascular problems (10 male, 10 female) participated. METHODS: All subjects received a treatment of continuous-wave ultrasound to the anterior forearm at a dosage of 1.5 W/cm2 for a duration of 5 minutes. The contralateral forearm served as the control and received identical treatment, except the ultrasound output remained at zero. Forearm blood flow was measured using venous occlusion plethysmography, and skin blood flow was measured using cutaneous laser-Doppler flowmetry before and after ultrasound administration, with the difference being muscle blood flow. RESULTS: No differences between the control arm and the ultrasound-treated arm were found for muscle, skin, and forearm blood flow. CONCLUSION AND DISCUSSION: These results suggest that administration of continuous-wave ultrasound at the prescribed dosage had no effect on skeletal muscle blood flow for up to 30 minutes posttreatment. Thus, muscle hyperemia is probably not the primary mechanism responsible for the clinical benefits seen following the use of ultrasound as a therapeutic modality.

Adult

The effect of cocaine and other local anesthetics on central dopaminergic neurotransmission.

The effects of cocaine on dopaminergic function in the rat were compared with those of other local anesthetics having an esteratic linkage (dimethocaine, procaine) or an amide linkage (lidocaine). By means of reverse-phase HPLC with electrochemical detection and gas chromatography-mass spectrometry, levels of dopamine (DA) and its metabolites 3-methoxytyramine (3-MT) and dihydroxyphenylacetic acid were quantified in the striatum, nucleus accumbens and prefrontal cortex after i.p. injection of the drugs or saline. Time course and dose response studies determined the effects of the drugs on these parameters of dopaminergic function. These studies provide strong evidence that the three esteratic local anesthetics cocaine, dimethocaine and procaine all increase the synaptic presence of DA, as reflected in increased levels of 3-MT and the ratio of 3-MT to DA, in the striatum, nucleus accumbens and prefrontal cortex. Surprisingly, procaine had an equal or greater effect than cocaine and dimethocaine on 3-MT levels and the ratio 3-MT/DA. The effects of these drugs on dihydroxyphenylacetic acid, an indicator of intraneuronal metabolism of DA, were more variable. However, the amidergic local anesthetic lidocaine did not affect DA metabolism. Although the exact mechanisms behind the dopaminergic activities of procaine and dimethocaine remain unknown, it is clear that these drugs, as well as cocaine, activate dopaminergic systems in the intact animal.

3,4-Dihydroxyphenylacetic Acid

Maternal and fetal brain and plasma levels of cocaine and benzoylecgonine after acute or chronic maternal intravenous administration of cocaine.

The effect of repeated i.v. administration of cocaine HCl (1.5, 3 or 6 mg/kg daily) from gestational day 8 through gestational day 18 was studied on maternal and litter parameters in the pregnant female Sprague-Dawley rat. These doses of cocaine had no significant effect on maternal weight gain or nutritional intake and did not significantly affect litter size. Levels of cocaine and its metabolite benzoylecgonine in the brain and plasma of the dams and their fetuses were measured on gestational day 18 at 1, 5, 20 or 60 min after a single injection or 11 daily i.v. injections of cocaine (6 mg/kg). The shape of the time courses for cocaine differed somewhat between dams and fetuses, with fetal plasma concentrations of cocaine initially being lower than those of their dams and then by 5 min becoming equivalent to those of their dams. Although plasma concentrations of cocaine soon equilibrated between dams and fetuses, plasma concentrations of benzoylecgonine did not. Interestingly, brain concentrations of cocaine did not differ between dams and fetuses. The most remarkable finding was that the relative distribution of cocaine between brain and plasma differed after chronic vs. acute treatment, with a relative shift in the distribution of cocaine from plasma to the brain in the fetuses, and with the exception of the earliest time point measured, in the dams after repeated dosing.

Animals

Prenatal exposure to methadone delays the development of striatal cholinergic neurons.

The effect of prenatal exposure to methadone via maternal osmotic minipumps on the expression of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) has been studied by light microscopy in the striatum of male and female rats. At postnatal day 10, rats of both sexes exhibit reduced intensity of ChAT-immunoreactive staining in striatal neurons in the methadone-treated group in comparison to either untreated or water-treated controls. Although the number and distribution of ChAT-immunoreactive neurons appear to be similar across all three groups, the size (cross-sectional area) of these neurons is significantly smaller in the methadone-treated animals. By postnatal day 22, there are no differences in the ChAT immunoreactivity of striatal neurons between the water-treated and methadone-treated animals. The size of these neurons in female animals of both treatment groups is significantly larger than those of male animals in the same groups at postnatal day 22. AChE histochemical staining is qualitatively similar between treatment groups in both age groups. Thus, prenatal exposure to methadone appears to produce a delay in the expression of ChAT in striatal neurons. It remains to be demonstrated whether these differences are a direct effect of methadone exposure or are a consequence of neonatal withdrawal.

Acetylcholine

Hypothermia blunts acetylcholine increase in CSF of traumatically brain injured rats.

Activation of muscarinic acetylcholine (ACh) receptors contributes to the pathophysiological consequences of moderate experimental traumatic brain injury (TBI). Hypothermia (30 degrees C) provides protection in experimental TBI. We measured ACh levels in CSF and plasma 5 min after moderate fluid percussion TBI under normothermic or hypothermic conditions, because ACh in the CSF has been correlated with the severity of behavioral deficits after TBI. Three groups were examined: TBI with hypothermic brain (30 degrees C), TBI with normothermic brain (37 degrees C), or sham TBI with normothermic brain (37 degrees C). ACh concentrations in CSF were significantly higher in 37 degrees C TBI rats, but not in 30 degrees C TBI rats compared to shams. ACh concentrations in plasma did not differ between groups. These results suggest that a contributing factor to the neuroprotective effects of moderate hypothermia in TBI may be related to the reduction of excessive ACh levels in the central nervous system following injury.

Acetylcholine

Does being in the military affect nurses' perceptions of work life?

This study was a causal comparative investigation of military and civilian nurses' perceptions of selected aspects of work life. The Work Environment Scale, the Maslach Burnout Inventory and the Michigan Job Satisfaction Scale were administered to civilian and military samples matched on selected demographic variables. MANOVA procedures failed to reveal significant differences on measures of burnout and morale. Although military nurses were significantly more satisfied with issues of pay and fringe benefits, civilian nurses reported significantly greater job satisfaction, peer cohesion, supervisory support, decision making, autonomy, task orientation and opportunity to be innovative. These findings and suggested changes are discussed with attention to differences between the military and civilian work setting.

Adult

Blockade of acute hypertensive response does not prevent changes in behavior or in CSF acetylcholine (ACH) content following traumatic brain injury (TBI).

There is evidence that the blood-brain barrier (BBB) is breached following traumatic brain injury (TBI), allowing the unregulated entry of circulating neuroactive substances into the central nervous system. As the traumatic episode is typically associated with an acute hypertensive event, which in itself may alter BBB status, the effects of the blockade of TBI-associated hypertension on injury-associated behavioral and cerebrospinal fluid (CSF) neurochemical changes were assessed in rats. Animals were injected with either saline or hexamethonium 15 min prior to a moderate fluid percussion injury while under light methoxyflurane anesthesia. This dose of hexamethonium was demonstrated to block the hypertensive response to TBI. Pretreatment with hexamethonium prevented neither acute nor more enduring behavioral deficits observed after TBI. Hexamethonium did not prevent TBI-associated increases in CSF acetylcholine (ACh) content in separate group of rats sampled 12 min following TBI. Furthermore, histological inspection indicated that hexamethonium did not prevent TBI-induced disruption of the BBB, as assessed by intravascular horseradish peroxidase (HRP). Thus, blockade of the hypertensive response to TBI does not afford behavioral protection nor does it prevent changes in the BBB or CSF ACh content following TBI. TBI is in itself sufficient to modify behavior, neurochemistry and BBB function in the absence of hypertension.

Acetylcholine