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Biomedical subjects

E MacDonald

Publications and source records attributed to E MacDonald.

At least 19 recordsLinked to original sources
PubMed2004

The effect of hydrogen peroxide concentration on the outcome of tooth whitening: an in vitro study.

AIM: This in vitro study examined the effect that various concentration of hydrogen peroxide (5-35%) had on tooth whitening. METHOD: Extracted third molars were sectioned and stained using a standardised tea solution to Vita shade C4. These stained specimens were then bleached with a series of gels containing 5, 10, 15 or 25% w/w hydrogen peroxide. Each specimen was bleached for a number of sessions with one session being defined as 3 x 10 min exposure. RESULTS: The number of applications of the various concentrations of bleaching gel varied from 12 applications for the 5% gel to one application for the 35% gel. Plotting the number of applications against hydrogen peroxide concentration showed an exponential response curve. CONCLUSIONS: The concentration of hydrogen peroxide in a proprietary bleaching gel had a marked effect on the number of applications required to produce an optimal shade outcome.

Algorithms↗
PubMed2002

Behavioral and neurochemical characterization of alpha(2A)-adrenergic receptor knockout mice.

Genetic manipulation of mice now provides new tools to evaluate the biological functions of the alpha(2)-adrenergic receptor (alpha(2)-AR) subtypes (alpha(2A), alpha(2B), and alpha(2C)). To investigate the role of the alpha(2A)-AR in the modulation of mouse primary behavioral characteristics and brain neurochemistry, mice with targeted inactivation of the gene for the alpha(2A)-AR were compared with wild-type C57BL/6 control animals. First, a comprehensive behavioral screen was employed to provide a detailed characterization of basic neurologic functions. Thereafter, the mice were analyzed in three models of anxiety, i.e. the elevated-plus maze test, the marble burying test and the open field test. The diurnal activity pattern of the mice was assessed in a 24-h locomotor activity test. Furthermore, receptor autoradiography of the brain was performed using the subtype-non-selective alpha(2)-AR antagonist radioligand [(3)H]RS-79948-197. Lack of the alpha(2A)-AR was associated with alterations in autonomic functions, including increased heart rate and piloerection. The mutant mice also exhibited impaired motor coordination skills, increased anxiety-like behavior and an abnormal diurnal activity pattern. In addition, neurochemical analysis of monoamine neurotransmitters revealed a considerable increase in brain norepinephrine turnover in mice lacking alpha(2A)-AR. Our results provide further support for the crucial role of the alpha(2A)-AR in modulating brain noradrenergic neurotransmission and many aspects of mouse behavior and physiology.

Animals↗
PubMed2001

Mechanics of solid tissue invasion by the mammalian pathogen Pythium insidiosum.

The relative significance of mechanical penetration versus the action of substrate-degrading enzymes during solid tissue invasion has not been established for any fungal disease. Pythium insidiosum is an oomycete fungus (or stramenopile) that causes a rare, but potentially lethal infection in humans and other mammalian hosts. Experiments with miniature strain gauges showed that single hyphal apices of this pathogen exert forces of up to 6.9 microN, corresponding to maximum pressures of 0.3 microN microm(-2) or MPa. Samples of cutaneous and subcutaneous tissue from fresh human cadavers displayed a mean strength (resistance to needle puncture) of 24 microN microm(-2), and a mean pressure of 30 microN microm(-2) was necessary to penetrate skin strips from slaughtered horses. These experiments demonstrate that P. insidiosum does not exert sufficient pressure to penetrate undamaged skin by mechanics alone, but must effect a decisive reduction in tissue strength by proteinase secretion.

Animals↗
PubMed2001

Psychosomatic disorders in pediatrics.

Psychosomatic symptoms are by definition clinical symptoms with no underlying organic pathology. Common symptoms seen in pediatric age group include abdominal pain, headaches, chest pain, fatigue, limb pain, back pain, worry about health and difficulty breathing. These, more frequently seen symptoms should be differentiated from somatoform or neurotic disorders seen mainly in adults. The prevalence of psychosomatic complaints in children and adolescents has been reported to be between 10 and 25%. These symptoms are theorized to be a response to stress. Potential sources of stress in children and adolescents include schoolwork, family problems, peer pressure, chronic disease or disability in parents, family moves, psychiatric disorder in parents and poor coping abilities. Characteristics that favour psychosomatic basis for symptoms include vagueness of symptoms, varying intensity, inconsistent nature and pattern of symptoms, presence of multiple symptoms at the same time, chronic course with apparent good health, delay in seeking medical care, and lack of concern on the part of the patient. A thorough medical and psychosocial history and physical examination are the most valuable aspects of diagnostic evaluation. Organic etiology for the symptoms must be ruled out. Appropriate mental health consultation should be considered for further evaluation and treatment.

Abdominal Pain↗
PubMed2001

Abrasion and stain removal by different manual toothbrushes and brush actions: studies in vitro.

BACKGROUND AND AIMS: A limited amount of data using flat trim multitufted toothbrushes shows that abrasion of substrate surfaces by a standard toothpaste varies dependent on filament stiffness and configuration; soft brushes producing the most abrasion. The aims of these studies in vitro were to assess toothpaste abrasion of acrylic and stain removal by 5 proprietary medium toothbrushes with different head filament arrangements, and a prototype brush with rectangular filaments. The prototype brush had a medium texture in the long axis and soft texture at right angles to the long axis. MATERIAL AND METHOD: Optically clear acrylic was used as the substrate for abrasion by a standard toothpaste. Loss of substrate was determined by profilometry after 5000, 10000, 15000 and 20000 linear or rotary brushing actions. Stain removal was determined spectrophotometrically from optically clear acrylic specimens stained by chlorhexidine tea soaking sequences. Stained specimens were brushed with water using linear or rotary actions and measurements taken every 10 s to 60 s. RESULTS: Abrasion was progressive with increasing strokes and the pattern for each brush and brush action was to a first approximation linear. Overall, abrasion was significantly greater with linear compared to rotary action. Also overall brushes differed in the abrasion produced with both actions and particularly at greater exposure times. Within brush differences for the two motions were all significant by 20000 strokes except for the prototype brush. Stain removal was progressive over time with each brush but the pattern was non-linear. For the proprietary brushes the rotary motion removed less stain. For the prototype brush more stain was removed with the rotary action. Overall brushes differed significantly in stain removal within each motion and for each motion most differences between the proprietary and prototype brushes reached significance. CONCLUSIONS: The differences between brushes for both abrasion and stain removal must in large part relate to the filament contact area with the substrate surface. Whilst the model may not be predictive of clinical differences, it could find use to establish minimum criteria for toothbrush action.

Acrylic Resins↗
PubMed2000

Dopamine release from pharmacologically distinct storage pools in rat striatum following stimulation at frequency of neuronal bursting.

The increase of dopamine overflow in the rat caudate and nucleus accumbens following repeated stimulation of the median forebrain bundle (MFB) at short intervals and the role of alpha-methyl-p-tyrosine (AMPT) and reserpine sensitive storage pools in evoked dopamine overflow were investigated by in vivo voltammetry. In contrast to stimulation at 30-s intervals and longer, stimulation of the MFB at 5-s intervals led to increased dopamine release following each consecutive stimulation. This effect was much larger in the caudate than in the nucleus accumbens. We consider that the increase in dopamine release is due to translocation of dopamine from a reserpine-sensitive storage pool and this accounts for the increase of the rate of refilling of the readily releasable pool. The shorter the intervals between stimulation and the higher the frequency (with a plateau at 30 Hz), then the greater the fraction of dopamine which originates from the reserpine-sensitive storage pool. Exocytotic release of dopamine from the AMPT-sensitive storage pool does not seem to depend on the intervals between stimulation. We propose that the vesicles in presynaptic dopaminergic terminals near the outer membrane are more sensitive to AMPT. Distantly located vesicles have a relatively higher sensitivity to reserpine. Experiments using repeated stimulation at as low a frequency as 10-20 Hz, revealed that this phenomenon may take place under physiological conditions following bursting of dopamine neurones.

Animals↗
PubMed2000

The chemical stain removal properties of 'whitening' toothpaste products: studies in vitro.

BACKGROUND: A considerable number of toothpastes are available as tooth whitening products. Most appear to contain ingredients that might remove extrinsic stains rather than change natural tooth colour. Extrinsic stain removal could be achieved by physical or chemical means. AIM: The purpose of this study was to measure the chemical stain removal properties of a range of whitening toothpaste products and experimental formulations using a standardised method in vitro. MATERIALS AND METHOD: 5 separate studies were conducted involving a total of 39 agents of which 28 were whitening products, 7 were experimental formulations, 2 were oxidising mouthrinses used as positive controls, 1 was a popular fluoride toothpaste product as a benchmark control, and 1 was water as the negative control. The formulations and controls varied in each study. The stain model was saliva/chlorhexidine/tea stain developed on optically clear acrylic to an optical density of at least 2.0. Groups of stained specimens were exposed to standard slurries or solutions of each test agent for 1 minute periods up to 5 minutes. Optical density readings were taken at each 1 minute time point. Analyses were based on per cent stain remaining after 5 minutes and time to 75% stain remaining. RESULTS: 3 toothpaste products achieved 100% stain removal by 5 minutes; 2 of these in 3 out of 4 studies in which they were used. 4 experimental formulations also achieved 100% stain removal. In general agents with high total stain removal also had short times to 75% stain remaining. The majority of agents tested had low total chemical stain removal and prolonged times to 75% stain remaining. A few agents were little different from water and several similar in effect to the conventional fluoride toothpaste. This method in vitro tests agents under the best case scenario conditions for chemical stain removal. CONCLUSION: Only a small number of the whitening toothpaste products have good chemical stain removal potential; the majority are unlikely to achieve their claimed benefits through chemical stain removal. There is clearly a need for further data on the actual effects of such products using both methods in vitro and particularly in vivo or in situ.

Acrylic Resins↗
PubMed2000

The effects of a specific alpha(2)-adrenoceptor antagonist, atipamezole, on cognitive performance and brain neurochemistry in aged Fisher 344 rats.

The present experiments investigated the effects of a specific and potent alpha(2)-adrenoceptor antagonist, atipamezole, on cognitive performance and neurochemistry in aged rats. Aged control Fisher 344 rats, which had lower activities of choline acetyltransferase in the frontal cortex, were impaired in the acquisition of the linear arm maze task both in terms of repetition errors and their behavioural activity (the speed of arm visits), and they needed longer time to complete this task as compared to adult control rats. Atipamezole treatment (0.3 mg/kg) facilitated the acquisition of this task in the aged rats as they committed fewer errors and completed the task more quickly than saline-treated aged control rats. A separate experiment indicated that atipamezole enhanced the turnover of noradrenaline both in the adult and aged rats, but this effect was more pronounced in the aged rats. Furthermore, atipamezole enhanced significantly the turnover of serotonin and dopamine only in the aged rats when analysed in the whole brain samples. As alpha(2)-adrenoceptor antagonists are known to alleviate akinesia in the experimental models of Parkinson's disease, the present results could be especially relevant for the development of palliative treatment for demented Parkinsonian patients.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2000

Blockade of muscarinic, rather than nicotinic, receptors impairs attention, but does not interact with serotonin depletion.

RATIONALE: The cholinergic system is considered to be essential for attention and the degeneration of the cholinergic system in Alzheimer's disease (AD) correlates with the cognitive decline seen in AD patients. The serotonergic system also degenerates in AD, but its role in the modulation of cognitive functions, especially attention, is somewhat unclear. OBJECTIVES: The present study investigated possible differences between cholinergic muscarinic and nicotinic receptor mediated mechanisms, the role of serotonin (5-HT) and the interaction between the cholinergic and serotonergic systems in the modulation of attention and response control. METHODS: The influences of cholinergic receptor blockade and 5-HT lesions on the performance of rats in the five-choice serial reaction time task were assessed. The 5-HT lesions were neurochemically verified. RESULTS: The neurochemical analysis indicated that the levels of 5-HT and 5-hydroxyindoleacetic acid were reduced quite specifically in the hippocampi, parieto-occipital and frontal cortices, and in the striatum of both p-chloroamphetamine (pCA) and 5, 7-dihydroxytryptamine (5,7-DHT) lesioned rats. The behavioural results showed that the pCA lesion caused a transient increase in impulsivity whereas the 5,7-DHT lesion temporarily reduced the motor activity and slightly impaired choice accuracy. Furthermore, the blockade of central muscarinic receptors by scopolamine (0.075 and 0. 150 mg/kg), but not nicotinic receptors by mecamylamine (1.0 or 3.0 mg/kg), impaired the choice accuracy, whereas the blockade of both muscarinic and nicotinic receptors interfered with motor activity, though possibly via peripheral mechanisms. Interestingly, mecamylamine (3.0 mg/kg) reduced impulsivity, whereas scopolamine slightly increased it. Serotonergic lesions did not make the rats more susceptible to the effects of cholinolytics on choice accuracy. CONCLUSIONS: 5-HT system is not essential for the modulation of attention, but it is important in the modulation of response control. Central muscarinic receptors are important in the modulation of attention, whereas central nicotinic receptors may be more essential in response control. The results do not support there being an interaction between the serotonergic and the cholinergic systems in the modulation of attention.

5,7-Dihydroxytryptamine↗
PubMed1999

Brain histamine levels and neocortical slow-wave activity in rats with portacaval anastomosis.

To determine whether the increased histamine levels in the brain of rats with portacaval anastomosis (PCA) are associated with the development of sleep disturbances during the light phase, the neocortical slow-wave activity of PCA-operated rats was examined with electroencephalography (EEG) 1 month and 6 months after the surgery. The tissue levels of histamine, tele-methylhistamine, 5-hydroxytryptamine (5-HT) (serotonin), and 5-hydroxyindole-3-acetic acid (5-HIAA) in frontal cortex were assayed by high-performance liquid chromatography 6 months after the surgery. PCA surgery led to changes in the synchronized, low-frequency, high-amplitude frontal cortex EEG activity recorded during the light phase. Delta-wave amplitude but not delta time was significantly decreased, whereas both spindle amplitude and spindling time were significantly decreased. There were also significant age-related changes, presented as increases in the duration of spindles and the amplitude of both delta waves and spindles. PCA-operated rats showed a change in the pattern of EEG activity with increasing age similar to sham-operated rats. This suggests that once established, the resetting of the systems regulating the sleep-waking behavior is being maintained with time. The tissue levels of both histamine and metabolite in the frontal cortex were increased, whereas the serotonin system showed only an increase in the level of the metabolite. There was a significant negative correlation between the spindling time and the tissue histamine levels. We suggest that histamine, which participates in the control of vigilance, sleep, and wakefulness, as well as in the modulation of circadian rhythmicity, may play a role in the development of sleep disturbances in rats with PCA.

Animals↗
PubMed1999

Comparison of the effects of acute and subchronic administration of atipamezole on reaction to novelty and active avoidance learning in rats.

The effects of an alpha2-adrenoceptor antagonist, atipamezole, on exploratory behaviour in a novel environment, spontaneous motor activity and active avoidance learning were studied after acute injection and continuous infusion (0.1 mg/kg h) for 24 h and 6-9 days in rats. The effects of atipamezole on biogenic amines and their main metabolites in brain were studied after an acute injection (0.3 mg/kg s.c.) and continuous infusion (0.1 mg/kg h) for 24 h and 10 days. The level of central alpha2-adrenoceptor antagonism and the drug concentration in blood and in the brain were measured after continuous infusion for 24 h and 10 days. In behavioural tests, atipamezole had no effect on spontaneous motor activity at any of the doses studied. However, after both acute administration and continuous 24-h infusion, atipamezole decreased exploratory behaviour in a staircase test, but no longer after 6 days of continuous infusion. Acute administration of atipamezole impaired performance in active avoidance learning tests causing a learned helplessness-like behaviour. When the training was started after 7 days of continuous infusion, atipamezole significantly improved active avoidance learning. There was a significant increase in the metabolite of noradrenaline (NA), 3-methoxy-4-hydroxyphenylethyleneglycol sulphate (MHPG-SO4), after 24 h but not any longer after 10 days of continuous atipamezole infusion, although the extent of central alpha2-adrenoceptor antagonism was unchanged and the atipamezole concentration present in brain was even elevated at 10 days compared to levels after 24-h infusion. In conclusion, these results reveal that acute and subchronic atipamezole treatments have different and even opposite effects on behaviour in novel, stressful situations. After acute treatment, atipamezole potentiates reaction to novelty and stress, causing a decrease in exploratory activity and impairment in shock avoidance learning. After subchronic treatment, there was no longer any effect on exploratory behaviour and, in fact, there was an improvement in the learning of a mildly stressful active avoidance test. The changes in behaviour occurred in parallel with attenuation in the MHPG-SO4-increasing effect, thus the suppressed behaviour in the present test conditions after acute atipamezole injection is associated with a major increase in central NA release. The results support the role of alpha2-adrenoceptors and noradrenergic system in reactions both to novelty and stress and have possible implications in cognitive functions as well as in depression.

Adrenergic alpha-Agonists↗
PubMed1999

Plasma catecholamine responses to four resistance exercise tests in men and women.

The plasma adrenaline ([A]) and noradrenaline ([NA]) concentration responses of nine men and eight women were investigated in four resistance exercise tests (E80, E60, E40 and E20), in which the subjects had to perform a maximal number of bilateral knee extension-flexion movements at a given cycle pace of 0.5 Hz, but at different load levels (80%, 60%, 40% and 20% of 1 repetition maximum, respectively). The four test sessions were separated by a minimal interval of 3 rest days. The number of repetitions (Repmax), the total work (Wtot) done normalized for the lean body mass and the heart rate (HR) responses were similar in the two groups in each test. In addition, no differences were found between the two groups in [A] and [NA] either before or after the exercise tests. The postexercise [NA], both in the men [10.8 (SD 7.0) nmol x l(-1)] and in the women [11.7 (SD 7.4) nmol x l(-1)], was clearly the highest in E20, where also the Repmax, WtOt, the total amount of integrated electromyograph activity in the agonist muscles and the peak postexercise blood lactate concentration [men 8.3 (SD 1.6) vs women 7.3 (SD 0.9) mmol x l(-1), ns] were significantly higher than in the other tests. Although the postexercise [A] in E20 both in the men [7.1 (SD 6.0) nmol x l(-1)] and in the women [5.2 (SD 2.0) nmol x l(-1)] were higher than in E80 [men 3.1 (SD 4.2), women 2.1 (SD 2.0) nmol x l(-l)] (P < 0.05), they were not significantly different from E60 [men 3.6 (SD 1.9), women 4.0 (SD 3.3) nmol x l(-1)] and E40 [men 3.8 (SD 4.1), women 5.8 (SD 4.0) nmol x l(-1)] in either group. The present study did not indicate any sex differences in performance and in plasma catecholamine responses in different exhausting resistance exercise tests performed with the knee extensor muscles. In both groups the plasma [NA] response was clearly the largest in the longest exercise with the greatest amount of muscle activity and work done, and with the largest blood lactate response. The differences in the plasma [A] responses between the exercises tended to be somewhat smaller.

Adult↗
PubMed1999

Central alpha1-adrenoceptors: their role in the modulation of attention and memory formation.

Adrenoceptors presently are classified into three main subclasses: alpha1-, alpha2-, and beta-receptors, each with three (perhaps more) subtypes. All three alpha1-adrenoceptor subtypes are present in rat brain. The purpose of this review is to assess the role of alpha1-adrenoceptors in the modulation of synaptic transmission and plasticity, as well as their ability to modulate higher cerebral functions, such as attentional and memory processes. However, since there are no truly subtype-specific agonists or antagonists available at present, it is virtually impossible to allocate a particular central effect to one or other of the subtypes. The activation of alpha1-adrenoceptors reduces the firing probability and glutamate release in the cornu ammonis of the hippocampus. Alpha1-Adrenoceptors may flexibly modulate weak and strong activation of the pyramidal neurones in the neocortex. Alpha1-Adrenoceptors play only a minor role in the modulation of long-term potentiation in the hippocampus, and may influence many brain functions also via non-neuronal mechanisms. since glial cells can express alpha1-adrenoceptors. At the behavioural level, the activation of alpha1-adrenoceptors promotes vigilance and influences working memory and behavioural activation, while having only a minor role in the modulation of long-term memory.

Animals↗
PubMed1999

Genetic alteration of the alpha2-adrenoceptor subtype c in mice affects the development of behavioral despair and stress-induced increases in plasma corticosterone levels.

alpha2-Adrenoceptors (alpha2-AR) modulate many central nervous system functions, such as regulation of sympathetic tone, vigilance, attention, and reactivity to environmental stressors. Three alpha2-AR subtypes (alpha2A, alpha2B, and alpha2C) with distinct tissue-distribution patterns are known to exist, but the functional significance of each subtype is not clear. Since specific, alpha2-AR subtype-selective pharmacological probes are not available, mice with genetically altered alpha2C-AR expression were studied in order to investigate the possible involvement of the alpha2C-AR in physiological and behavioral responses to acute and repeated stress. A modified version of Porsolt's forced swimming test was used to assess the possible effects of altered alpha2C-AR expression on the development of behavioral despair. alpha2C-Overexpression increased and the lack of alpha2C-AR (alpha2C-KO) decreased the immobility of mice in the forced swimming test, ie alpha2C-AR expression appeared to promote the development of behavioral despair. In addition, alpha2C-KO was associated with attenuated elevation of plasma corticosterone after different stressors, and overexpression of alpha2C-ARs was linked with increased corticosterone levels after repeated stress. Moreover, the brain dopamine and serotonin balance, but not norepinephrine turnover, was dependent on alpha2C-AR expression, and the expression of c-fos and junB mRNA was increased in alpha2C-KO mice. Since alpha2C-KO produced stress-protective effects, and alpha2C-AR overexpression seemed to promote the development of changes related to depression, it is suggested that a yet-to-be developed subtype-selective alpha2C-AR antagonist might have therapeutic value in the treatment of stress-related neuropsychiatric disorders.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Hormonal changes during parturition in heifers and goats are related to the phases and severity of labour.

Parturition is a natural event that involves stress and pain for the mother. We thus hypothesized that levels of stress hormones measured during parturition could reflect levels reached in response to severe discomfort and pain of other kinds as well. The aim of this study was therefore to determine whether plasma concentrations of cortisol, adrenaline, noradrenaline, beta-endorphin, met-enkephalin, vasopressin and oxytocin vary depending on the phase and severity of labour in dairy heifers (ten) and dairy goats (six), and how these hormones interact with each other. Blood samples were taken once a day for 3 days before labour and for 3 days afterwards and at predetermined phases during labour. All heifers delivered one calf and five of them needed obstetrical assistance. Two of the goats delivered one kid, and four had twins; all kidded without help. The cortisol concentration peaked when the calf and the first kid were born. In the heifers, plasma adrenaline increased after delivery, while the noradrenaline concentration did not change significantly in heifers that needed assistance, but increased during expulsion in heifers calving without help. In the goats, adrenaline and noradrenaline concentrations increased in association with expulsion of the first kid. The beta-endorphin concentration increased during labour in goats. In heifers that needed assistance, beta-endorphin concentration increased 1 h after labour but there was no change in heifers that did not need assistance. The met-enkephalin concentration was elevated during expulsion in heifers and fluctuated in the goats. Both oxytocin and vasopressin increased during expulsion in both groups of heifers, but vasopressin increased four times more in heifers needing assistance. In the goats, oxytocin reached its highest levels just as the feet of the first kid became visible, and vasopressin peaked as the head emerged. Parturition took longer in heifers that needed assistance than in those that did not. It is concluded that, even though the pattern of change differed between hormones during labour, the changes were related to the phases of labour. A longer labour therefore meant that the hormone concentrations stayed elevated for longer. Vasopressin reached high levels in goats and was the only hormone for which plasma concentrations were higher in heifers that needed assistance than in those that did not, indicating that this hormone is released in order to deal with the pain-related stress associated with labour.

Analysis of Variance↗
PubMed1998

No change of brain extracellular catecholamine levels after acute catechol-O-methyltransferase inhibition: a microdialysis study in anaesthetized rats.

Catechol-O-methyltransferase inhibitors have been newly introduced as adjunct drugs to the levodopa/dopa decarboxylase inhibitor therapy in Parkinson's disease. When given alone, catechol-O-methyltransferase inhibitors seem to affect behaviour. We wanted to determine whether the concentrations of free amine would be increased by catechol-O-methyltransferase inhibition with tolcapone and underpin the positive behavioural effects. To this end, dopamine and noradrenaline levels were analyzed in the microdialysis perfusion fluid collected from several brain regions in chloral hydrate anaesthetized rats. We also analyzed the turnover rate of catecholamines in the brain after single doses of tolcapone and entacapone using the alpha-methyl-p-tyrosine method. On their own, tolcapone (at 10 or 30 mg/kg) did not elevate dopamine or noradrenaline levels in any brain region studied although the formation of catechol-O-methyltransferase-dependent metabolites was strongly reduced. Neither tolcapone nor entacapone (at 30 mg/kg) affected the turnover rate of catecholamines. It seems that catechol-O-methyltransferase inhibitors do not alter behaviour by elevating extracellular levels of free catecholamines levels but other explanations are needed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Norcocaine is a potent modulator of haemodynamic responses, plasma catecholamines and cardiac hormone release in conscious rats.

We examined the effects of intravenously administered cocaine and norcocaine on the haemodynamics, the plasma immunoreactive atrial natriuretic peptide (ANP), the N-terminal peptide of proANP (NT-ANP) and the plasma catecholamine levels in conscious, chronically cannulated Sprague-Dawley rats. Cocaine caused an immediate significant peak rise in the mean arterial pressure which was followed by a dose-dependent sustained pressor response. Cocaine also decreased the heart rate and increased the right atrial pressure. Norcocaine at a dose of 1 mg/kg maximally decreased the heart rate which did not recover to the basal level within 15 min. Norcocaine (1 mg/kg) did not affect the right atrial pressure but with a dose of 3 mg/kg an elevation of 2.2 +/- 0.3 mmHg (P < 0.005) was observed which did not recover to the control level during the 30 min study period. Plasma immunoreactive ANP and NT-ANP levels increased significantly in a dose-dependent manner after the injection of cocaine. Norcocaine treatments also resulted in significant correlations between ANP or NT-ANP levels and haemodynamic variables, especially between the right atrial pressure and the plasma immunoreactive ANP levels (r = 0.58, n = 28, P < 0.005). Cocaine and norcocaine enhanced the plasma adrenaline levels but norcocaine, already at a dose of 1 mg/kg, caused a maximal increase in the plasma adrenaline levels. The long lasting increase in the right atrial pressure after norcocaine and the decrease in the heart rate after higher doses of cocaine suggest the role for this metabolite, or a further metabolite of norcocaine, in the cardiovascular and haemodynamic responses to cocaine seen in conscious rats.

Animals↗