Behavioural assays of the effects of antidepressant drug treatment on the functioning of catecholamine systems

The effects of antidepressant drugs on central beta-adrenergic and dopaminergic receptor function were investigated using the anorexic effects of low doses of amphetamine and apomorphine as assays of beta-adrenergic function and presynaptic dopamine function respectively. Anorexia was typically examined using a microstructural analysis of feeding, which was validated observationally. Amphetamine anorexia was characterized by a decrease in eating time and an increase in eating rate. At 0.5 mg/kg both beta-adrenergic and dopaminergic antagonists reversed anorexic effects, whilst anorexia at 1.0 mg/kg was reversed by dopaminergic antagonists only. An enhancement of amphetamine anorexia was seen following acute desmethylimipramine treatment! this effect was exactly compensated for over chronic treatment, implying no net change at beta-adrenergic synapses. However, applying amphetamine intracranially showed that approximately 75% of the acute enhancement of amphetamine anorexia was mediated peripherally, suggesting an attenuation of beta-receptor function during chronic antidepressant drug treatment. Some further data suggested that an alpha-adrenergic change could also have contributed to the antidepressant drug-induced attenuation of anorexia. Low doses of apomorphine, specific for presynaptic dopamine receptors, induced an anorexia characterized by decreases in both eating time and eating rate. The dopamine receptor antagonists haloperidol and thioridazine reversed apomorphine anorexia by reversing eating time but not eating rate. Administration of apomorphine into nuclei A9 and A10 reduced total food intake and eating time but not eating rate. These findings imply that presynaptic dopamine receptors mediate the effects of apomorphine on eating time. Acute treatment with desmethylimipramine, enhanced apomorphine anorexia. During chronic treatment the apomorphine-induced reduction in eating time was sometimes attenuated, suggesting a presynaptic dopamine receptor subsensitivity. Anorexia was also enhanced following acute desmethylimipramine treatment with intracranial administration of apomorphine. Again, there was no clear evidence of subsensitivity following chronic treatment, but some evidence for subsensitivity in nucleus A10 during withdrawal. The significance of a reduced beta-receptor function and an increased dopamine function following chronic antidepressant drug treatment are discussed in relation to the biological basis of depression

Perceived control, locus of control and preparatory information: effects on the perception of an acute pain stimulus

This study investigated the effects of differences in a pre-procedure briefing (providing or withholding preparatory information and explicit control) on the perception of the second of two identical acute pain stimuli. 61 healthy participants were allocated to one of three conditions: Information + Control (I+C), Information - No Control (I-NC) or No information - No Control (NINC). Baseline measures of Pressure Pain Threshold (PPT) and pain rating using Visual Analogue Scales (VAS) were taken, as was a measure of general internal/external Locus of Control (LOC). Participants were read the briefing and subjected to a second pain stimulus of identical intensity to their baseline measures. Participants rated the second stimulus using the VASs, and compared it to the first using comparison scales. Results show that differences in a pre-procedure briefing significantly altered participants' perception of the pain stimulus. Participants in the I-NC group rated the second stimulus more painful than the first, and participants in the NI-NC group rated the second stimulus as less painful than the first. There is also suggestive evidence that these differences may relate to individual LOC style. We recommend encouragement of patient participation to engender at least the perception of control in clinical situations involving acutely painful procedures

Non-perturbative structure of the polarized nucleon sea

We investigate the flavour and quark-antiquark structure of the polarized nucleon by calculating the parton distribution functions of the nucleon sea using the meson cloud model. We find that the SU(2) flavor symmetry in the light antiquark sea and quark-antiquark symmetry in the strange quark sea are broken, {\it i.e.} \Delta\ubar < \Delta \dbar and \Delta s < \Delta \sbar. The polarization of the strange sea is found to be positive, which is in contradiction to previous analyses. We predict a much larger quark-antiquark asymmetry in the polarized strange quark sea than that in the unpolarized strange quark sea. Our results for both polarized light quark sea and polarized strange quark sea are consistent with the recent HERMES data.Comment: RevTex, 17 pages plus 8 PS figure

x−x-dependence of the quark distribution functions in the χ\chiCQMconfig_{{\rm config}}

Chiral constituent quark model with configuration mixing (\chiCQM_{{\rm config}}) is known to provide a satisfactory explanation of the ``proton spin problem'' and related issues. In order to enlarge the scope of \chiCQM_{{\rm config}}, we have attempted to phenomenologically incorporate x-dependence in the quark distribution functions. In particular, apart from calculating valence and sea quark distributions q_{{\rm val}}(x) and \bar q(x), we have carried out a detailed analysis to estimate the sea quark asymmetries \bar d(x)-\bar u(x), \bar d(x)/\bar u(x) and \frac{\bar d(x)-\bar u(x)}{u(x)-d(x)} as well as spin independent structure functions F_2^p(x)-F_2^n(x) and $F_2^n(x)/F_2^p(x)$ as functions of $x$. We are able to achieve a satisfactory fit for all the above mentioned quantities simultaneously. The inclusion of effects due to configuration mixing have also been examined in the case F_2^p(x)-F_2^n(x) and F_2^n(x)/F_2^p(x) where the valence quark distributions dominate and it is found that it leads to considerable improvement in the results. Further, the valence quark structure has also be tested by extrapolating the predictions of our model in the limit x \to 1 where data is not available.Comment: 20 pages, 7 figures. To appear in Eur. Phys. J.

Central and peripheral contributions to the enhancement of amphetamine anorexia by des-methylimipramine (DMI)

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Bitters: Time for a New Paradigm

In plant-based medical systems, bitter tasting plants play a key role in managing dyspepsia. Yet when it comes to defining their mechanism of activity, herbalists and pharmacologists are split between two theories: one involves cephalic elicited vagal responses while the other comprises purely local responses. Recent studies indicate that bitters elicit a range of cephalic responses which alter postprandial gastric phase haemodynamics. Caffeine and regular coffee (Coffea arabica semen, L.) increase heart rate whereas gentian (Gentiana lutea radix, L.) and wormwood (Artemisia absinthium herba L.) increase tonus in the vascular resistance vessels. Following meals increased cardiac activity acts to support postprandial hyperaemia and maintain systemic blood pressure. The increased vascular tonus acts in parallel with the increased cardiac activity and in normal adults this additional pressor effect results in a reduced cardiac workload. The vascular response is a sympathetic reflex, evident after 5 minutes and dose dependent. Thus gentian and wormwood elicit cephalic responses which facilitate rather than stimulate digestive activity when postprandial hyperaemia is inadequate. Encapsulated caffeine elicits cardiovascular responses indicating that gastrointestinal bitter receptors are functionally active in humans. However, neither encapsulated gentian nor wormwood elicited cardiovascular responses during the gastric phase. These findings provide the platform for a new evidence-based paradigm

Functional outcome following stroke in children

The aim of this study was to describe the functional consequences of childhood stroke in terms of activity limitation and to explore the relationship between extent of brain damage, impairment, and functional sequelae. A further aim was to describe the health of the parents of these children. Seventeen children and adolescents with cerebral infarction in the territory of the middle cerebral artery were enrolled in the study. A new activity limitation measure with a 4-point Likert scale (the Paediatric Stroke Activity Limitation Measure) was designed to examine the degree of difficulty experienced by the children in daily activities. The relationship between activity limitation scores, standardized health-related quality of life assessment (Child Health Questionnaire), extent of brain damage, and results of a comprehensive neurologic examination (Pediatric Stroke Outcome Measure) were investigated. Parent health was assessed using the Short-Form 36 General Health Survey. Activity limitation was evident in the domains of education, self-care, and motor skills. There was very good interobserver agreement using the new activity limitation scale between the occupational therapist and pediatric neurologist (Cohen’s kappa = 0.88). In comparison with population norms, the subjects scored below average in both physical and psychologic health. There was a clear relationship between radiologically apparent extent of brain damage, degree of impairment, and functional outcome. Parental health also rated generally lower than expected. This exploratory study suggests that both children who have had a stroke and their parents have significant and wide-ranging health needs.</p