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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
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1992

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↗
PubMed1992

The effect of cobrotoxin on cholinergic neurons in the mouse.

By using multiple time-point constant-rate infusions of deuterium-labeled phosphorylcholine, appropriate kinetic parameters were obtained for use in the calculation of the turnover rate of acetylcholine (TRACh) in selected mouse brain regions. After obtaining these data, the relationship between the analgesic agent cobrotoxin (CT) and the activity of central cholinergic neurons was investigated by determination of TRACh in selected mouse brain regions 3 hours following intracerebroventricular (i.c.v.) injection of CT. There were no obvious changes in the concentrations of ACh and choline (Ch) in the cortex, hippocampus, hypothalamus, midbrain, striatum, or thalamus of the mouse after injection of an analgesic dose of CT (2 micrograms, i.c.v.). TRACh in the thalamus and the striatum were significantly increased, as compared to controls. On the other hand, i.c.v. injection of CT was found to significantly reduce TRACh in the hippocampus and midbrain. These results suggest that the activity of hippocampal and midbrain cholinergic neurons is suppressed by CT, whereas the activity of striatal and thalamic cholinergic neurons is increased by CT at a time when a maximum analgesic response to CT is expressed.

Acetylcholine↗
PubMed1991

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

The effect of prenatal exposure to methadone via maternal osmotic minipumps was studied on brain regional acetylcholine (ACh) turnover and dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytryptamine, 5-HT) and their metabolites in 21-day-old female and male rats. ACh content was not affected in any region studied. However, the turnover rate of ACh (TRAch) was increased significantly in the striata and parietal cortices of both sexes. Two gender-specific changes were observed: a profound decrease in hypothalamic TRACh in the females and an increase in hippocampal TRACh in the males. No changes were observed in TRACh in the medulla-pons or the frontal cortex of either sex. The reduction in TRACh was accompanied by a threefold increase in DA content in the hypothalamus of the methadone-exposed females. No other changes were observed in DA, NE, or 5-HT, save for increased 5-HT content in the medulla-pons of the male methadone-exposed rats. Thus, prenatal methadone exposure produces several lingering changes in cholinergic function, many of which were not apparent in the immediate postnatal period. Although striatal ACh content was no longer reduced in methadone-exposed rats, striatal cholinergic function remains disrupted. It remains to be proven whether these differences are a direct effect of methadone exposure or are a consequence of neonatal withdrawal.

Acetylcholine↗
PubMed1991

Nurse burnout: work related and demographic factors as culprits.

This study was an examination of the combined ability of perceived work environment, demographic, and work-related variables to predict burnout among 314 nurses at a large metropolitan hospital. The three dimensions of burnout measured were emotional exhaustion, depersonalization, and personal accomplishment. High work pressure and low work involvement and supervisor support predicted emotional exhaustion. Task orientation, work pressure, work involvement, and age predicted both depersonalization and personal accomplishment. Burnout among nurses on each of the three work shifts also was examined. Results are discussed from the perspective of how to decrease or to prevent burnout among nurses.

Adult↗
PubMed1990

The effect of prenatal exposure to methadone on neurotransmitters in neonatal rats.

The effect of prenatal exposure to methadone via maternal osmotic minipumps was studied on neurotransmitter content of 4-day-old male and female rats. Several sex-related differences were observed in brain regional neurotransmitter content. Prenatal exposure to methadone produced only selective changes in brain regional neurotransmitter content. Exposure to methadone in doses sufficient to produce maternal and fetal dependence selectively reduced striatal acetylcholine content and produced a sex-dependent change in hindbrain acetylcholine.

Acetylcholine↗
PubMed1990

The effect of M1 muscarinic blockade on behavior and physiological responses following traumatic brain injury in the rat.

Dicyclomine (1 mg/kg or 10 mg/kg), scopolamine (1 mg/kg), or saline was administered intraperitoneally to rats 15 min prior to moderate fluid percussion brain injury. A variety of reflexes and responses were measured up to 60 min following injury, and body weight and several neurological measures were taken daily up to 10 days following injury. All 3 antimuscarinic treatments reduced the duration of transient behavioral suppression as assessed by these measures. It appears that blockade of the M1 muscarinic receptor can attenuate transient behavioral suppression associated with concussive brain injury. Thus, stimulation of M1 muscarinic receptors may mediate components of reversible traumatic unconsciousness following cerebral concussion. No differences were observed between saline and antimuscarinic treatments in the incidence or duration of apnea following injury. Scopolamine pretreatment significantly elevated heart rate prior to injury, but had no significant effect on the responses of heart rate and blood pressure to experimental concussion. Both doses of dicyclomine significantly reduced resting heart rate, but unlike scopolamine, significantly enhanced the cardiovascular response to fluid percussion injury. Antimuscarinic treatment significantly reduced body weight loss and certain motor deficits, including beam balance and beam walk performance, following concussive head injury. Scopolamine and both doses of dicyclomine appeared to be equally effective in reducing long-term deficits. Data from these experiments indicate that at least some of the long-term behavioral deficits following moderate levels of brain injury may involve the binding of acetylcholine to M1 muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The effect of acetylcholine depletion on behavior following traumatic brain injury.

Rats were injected with either saline; A-4 (40 mg/kg, i.p.), a bis tertiary amine derivative of hemicholinium-3; or A-5 (50 micrograms/kg, i.p.), a bis quaternary amine derivative of hemicholinium-3, 1 h prior to moderate fluid percussion brain injury. A variety of reflexes and responses were measured up to 60 min following injury, and body weight and several neurological measures were taken daily up to 10 days following injury. Pretreatment with either A-4 or A-5 significantly attenuated components of transient behavioral suppression, as well as more enduring deficits in body weight and beam walk and beam balance performance. A-4 administered prior to fluid percussion was found to reduce striatal, but not pontine, acetylcholine content. A-5 did not significantly reduce acetylcholine content in either area. Both A-4 and A-5 pretreatment prevented a significant increase in acetylcholine content in the cerebrospinal fluid following fluid percussion injury; however, only A-5 significantly reduced plasma acetylcholine content. These results confirm cholinergic involvement in the production of both transient and longer-lasting behavioral deficits following traumatic brain injury. Furthermore, traumatic brain injury may allow plasma constituents to gain access to the central nervous system.

Acetylcholine↗
PubMed1990

The effect of cholinergic manipulations on the analgesic response to cobrotoxin in mice.

Intracerebroventricular (i.c.v.) injection of cobrotoxin (CT), a neurotoxin isolated from the venom of Naja naja atra, produced an antinociceptive response in mice as measured by the tail-flick test. This effect of CT was blocked by systemic administration of atropine, but not by methylatropine or naloxone. Depletion of central acetylcholine (ACh) by hemicholinium-3 (HC-3) blocked the antinociceptive action of cobrotoxin. These results suggest that central cholinergic neurons are important for the mediation of the antinociceptive properties of cobrotoxin.

Acetylcholine↗
PubMed1989

The effects of morphine and traumatic brain injury on central cholinergic neurons.

This study examined the effects of morphine and fluid percussion traumatic brain injury (TBI) on the activity of cholinergic neurons in specific areas of the rat brain 12 min after injury. Acetylcholine (ACh) turnover, used as an index of cholinergic neuronal activity, was determined using gas chromatography-mass spectrometry. Although morphine administration alone in general did not significantly affect ACh content and turnover in specific brain areas, morphine administered prior to TBI either prevented injury-induced changes in ACh turnover (dorsal pontine tegmentum) or actually reduced the rate constant for ACh utilization (kACh) and the turnover rate of ACh (TRACh) following injury (thalamus, amygdala, cingulate/frontal cortex, and hippocampus). Thus, the protective effects of morphine against enduring behavioral deficits following TBI may involve the inhibition of central cholinergic neurons.

Acetylcholine↗
PubMed1989

Life stress and lymphocyte alterations among patients with rheumatoid arthritis.

The relation between life stress and immune parameters was investigated for 33 female rheumatoid arthritis (RA) patients interviewed during three routine monthly clinic checkups. Life stress from major and minor events, coping efficacy, and self-reported psychological distress were assessed, and immunofluorescence of T-cells and B-cells was performed on the blood drawn during each visit. Small stressful events were positively related to the proportion of circulating B-cells, psychological distress was inversely related to proportion of circulating T-cells, and major life events were associated with lower T-helper/T-suppressor cell ratios.

Adaptation, Psychological↗
PubMed1988

The effect of cocaine on hippocampal cholinergic and noradrenergic metabolism.

Rats treated with L-cocaine HCl exhibited an increase in hippocampal acetylcholine turnover, as measured by a mass fragmentographic technique. Furthermore, the ratio of hippocampal 3-methoxy-4-hydroxyphenylethyleneglycol to norepinephrine increased significantly. Possible mechanisms of the increased cholinergic activity are discussed.

Acetylcholine↗
PubMed1988

The effect of concussive head injury on central cholinergic neurons.

This study examined the effect of fluid percussion head injury on the activity of cholinergic neurons in specific brain areas of the rat 12 min, 4 h and 24 h following injury. Acetylcholine (ACh) turnover, used as an index of cholinergic neuronal activity, was determined using a gas chromatographic-mass spectrometric technique. The most striking changes in cholinergic activity were observed in the dorsal pontine tegmentum, where concussive head injury produced an increase in ACh turnover 12 min and 4 h following injury. This area has been previously associated with behavioral changes observed following concussive injury. ACh turnover in the thalamus, a region to which pontine cholinergic neurons project, also tended to increase 4 h following injury. On the other hand, ACh turnover tended to decrease in the amygdala 4 h following injury. Although there were no significant changes in hippocampal ACh content or turnover following injury. ACh content did tend to increase in that brain region 12 min following injury. There were no significant effects of injury on cholinergic neurons in the cingulate/frontal cortex. These changes in cholinergic neuronal activity may contribute to the neurological deficits following concussive injury. In particular, activation of cholinergic neurons in the pontine region may contribute to components of behavioral suppression associated with reversible traumatic unconsciousness. More generalized changes in cholinergic function may lead to the production of more chronic deficits.

Acetylcholine↗
PubMed1988

Basal forebrain carbachol injection reduces cortical acetylcholine turnover and disrupts memory.

Injection of the cholinergic agonist carbachol into the region of cholinergic cell bodies in the basal forebrain decreases the turnover rate of acetylcholine in the cortex of the rat, as measured by a mass fragmentographic technique. Moreover, this treatment has been found to increase the number of working memory errors committed as measured in the 8-arm radial maze. These results suggest an inhibitory cholinergic mechanism on the cell bodies of basal forebrain neurons which may be important in memory and the treatment of Alzheimer's disease.

Acetylcholine↗