Extracellular single unit recording techniques were used to study the effects of both acute and repeated oral neuroleptic administration on the in vivo activity of rat A9 and A10 dopaminergic (DA) neurons. All antipsychotic drugs examined acutely (haloperidol, l-sulpiride, chlorpromazine, and clozapine) increased the number of spontaneously firing DA neurons in both A9 and A10 compared to controls. Repeated (21 day) treatment with haloperidol, l-sulpiride, and chlorpromazine (antipsychotic drugs which can cause extrapyramidal side effects) markedly reduced the number of active DA cells below control levels in both regions. The "silent" DA neurons were in an apparent state of tonic depolarization inactivation since they could be induced to discharge by the microiontophoretic application of the inhibitory neurotransmitter gamma-aminobutyric acid, but not the excitatory amino acid glutamate. The depolarization inactivation observed may be specific for antipsychotic drugs since a non-neuroleptic phenothiazine (promethazine), the inactive isomer of sulpiride (d-sulpiride), and a tricyclic antidepressant (desmethylimipramine) neither increased DA activity when given acutely nor induced depolarization inactivation when administered repeatedly. In contrast to the other drugs tested, repeated treatment with clozapine (an effective antipsychotic drug which does not produce extrapyramidal side effects) resulted in the depolarization inactivation of A10 neurons but not A9 cells. These data suggest that neuroleptics which can induce extrapyramidal side effects produce depolarization inactivation of both A9 and A10 neurons whereas antipsychotic drugs which lack this property inactivate only A10 neurons. It is suggested that the time-dependent development of A9 DA neuron inactivation induced by repeated neuroleptic treatment may provide a mechanism for understanding the delayed onset of extrapyramidal side effects often observed with these drugs.

https://www.jneurosci.org/content/jneuro/3/8/1607.full.pdf

Typical and atypical neuroleptics: differential effects of chronic administration on the activity of A9 and A10 midbrain dopaminergic neurons

Partial lesions of the dopaminergic nigrostriatal system in rat brain: biochemical characterization

Systematic reviews and meta-analyses represent the uppermost ladders in the hierarchy of evidence. Systematic reviews/meta-analyses suggest preliminary or satisfactory clinical evidence for agnus castus (Vitex agnus castus) for premenstrual complaints, flaxseed (Linum usitatissimum) for hypertension, feverfew (Tanacetum partenium) for migraine prevention, ginger (Zingiber officinalis) for pregnancy-induced nausea, ginseng (Panax ginseng) for improving fasting glucose levels as well as phytoestrogens and St John's wort (Hypericum perforatum) for the relief of some symptoms in menopause. However, firm conclusions of efficacy cannot be generally drawn. On the other hand, inconclusive evidence of efficacy or contradictory results have been reported for Aloe vera in the treatment of psoriasis, cranberry (Vaccinium macrocarpon) in cystitis prevention, ginkgo (Ginkgo biloba) for tinnitus and intermittent claudication, echinacea (Echinacea spp.) for the prevention of common cold and pomegranate (Punica granatum) for the prevention/treatment of cardiovascular diseases. A critical evaluation of the clinical data regarding the adverse effects has shown that herbal remedies are generally better tolerated than synthetic medications. Nevertheless, potentially serious adverse events, including herb-drug interactions, have been described. This suggests the need to be vigilant when using herbal remedies, particularly in specific conditions, such as during pregnancy and in the paediatric population. Copyright © 2016 John Wiley & Sons, Ltd.

A Critical Approach to Evaluating Clinical Efficacy, Adverse Events and Drug Interactions of Herbal Remedies.

Polyphenols are found in plant-based foods and beverages, notably apples, berries, citrus fruit, plums, broccoli, cocoa, tea and coffee, and many others. There is substantial epidemiological evidence that a diet high in polyphenol-rich fruit, vegetables, cocoa and beverages protects against developing cardiovascular disease and type 2 diabetes. The absorption and metabolism of these compounds has been well described and, for many, the gut microbiota play a critical role in absorption; taking into consideration the parent compound and the metabolites from colon bacteria catabolism, more than 80% of a dose can be absorbed and ultimately excreted in the urine. Common polyphenols in the diet are flavanols (cocoa, tea, apples, broad beans), flavanones (hesperidin in citrus fruit), hydroxycinnamates (coffee, many fruits), flavonols (quercetin in onions, apples and tea) and anthocyanins (berries). Many intervention studies, mechanistic in vitro data and epidemiological studies support a role for polyphenols against the development of chronic diseases. For example, flavanols decrease endothelial dysfunction, lower blood pressure and cholesterol, and modulate energy metabolism. Coffee and tea both reduce the risk of developing type 2 diabetes, through action of their constituent polyphenols. Despite extensive research, the exact mechanisms of action of polyphenols in the human body have not been decisively proven, but there is strong evidence that some targets such as nitric oxide metabolism, carbohydrate digestion, and oxidative enzymes are important for health benefits. Consumption of polyphenols as healthy dietary components is consistent with the advice to eat five or more portions of fruit and vegetables per day, but it is currently difficult to recommend what ‘doses’ of specific polyphenols should be consumed to derive maximum benefit.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/nbu.12278

The role of polyphenols in modern nutrition.

Various criteria used to define atypical antipsychotic drugs include: 1) decrease, or absence, of the capacity to cause acute extrapyramidal motor side effects (acute EPSE) and tardive dyskinesia (TD); 2) increased therapeutic efficacy reflected by improvement in positive, negative, or cognitive symptoms; 3) and a decrease, or absence, of the capacity to increase prolactin levels. The pharmacologic basis of atypical antipsychotic drug activity has been the target of intensive study since the significance of clozapine was first appreciated. Three notions have been utilized conceptually to explain the distinction between atypical versus typical antipsychotic drugs: 1) dose-response separation between particular pharmacologic functions; 2) anatomic specificity of particular pharmacologic activities; 3) neurotransmitter receptor interactions and pharmacodynamics. These conceptual bases are not mutually exclusive, and the demonstration of limbic versus extrapyramidal motor functional selectivity is apparent within each arbitrary theoretical base. This review discusses salient distinctions predominantly between prototypic atypical and typical antipsychotic drugs such as clozapine and haloperidol, respectively. In addition, areas of common function between atypical and typical antipsychotic drug action may also be crucial to our identification of pathophysiological foci of the different dimensions of schizophrenia, including positive symptoms, negative symptoms, and neurocognitive deficits.

Mechanisms of action of atypical antipsychotic drugs: a critical analysis

Background

The popularity of botanical products is on the rise in Europe, with consumers using them to complement their diets or to maintain health, and products are taken in many different forms (e.g. teas, juices, herbal medicinal products, plant food supplements (PFS)). However there is a scarcity of data on the usage of such products at European level. Objective

To provide an overview of the characteristics and usage patterns of PFS consumers in six European countries. Design

Data on PFS usage were collected in a cross-sectional, retrospective survey of PFS consumers using a bespoke frequency of PFS usage questionnaire. Subjects/setting

A total sample of 2359 adult PFS consumers from Finland, Germany, Italy, Romania, Spain and the United Kingdom. Data analyses

Descriptive analyses were conducted, with all data stratified by gender, age, and country. Absolute frequencies, percentages and 95% confidence intervals are reported. Results

Overall, an estimated 18.8% of screened survey respondents used at least one PFS. Characteristics of PFS consumers included being older, well-educated, never having smoked and self-reporting health status as “good or very good”. Across countries, 491 different botanicals were identified in the PFS products used, with Ginkgo biloba (Ginkgo), Oenothera biennis (Evening primrose) and Cynara scolymus (Artichoke) being most frequently reported; the most popular dose forms were capsules and pills/tablets. Most consumers used one product and half of all users took single-botanical products. Some results varied across countries. Conclusions

The PlantLIBRA consumer survey is unique in reporting on usage patterns of PFS consumers in six European countries. The survey highlights the complexity of measuring the intake of such products, particularly at pan-European level. Incorporating measures of the intake of botanicals in national dietary surveys would provide much-needed data for comprehensive risk and benefit assessments at the European level.

/pdf/usage-of-plant-food-supplements-across-six-european-4zf785hal4.pdf

Usage of plant food supplements across six European countries: findings from the PlantLIBRA consumer survey.

Functional interaction between rat substantia nigra and striatum: GABA and dopamine interrelation

Morphine injected intraperitoneally into mice produces analgesia and running activity that appear to be determined by genetic influence (Castellano & Oliverio, 1975). For example, C 57 RL/J (C 57) mice show high locomotor response when running behaviour is considered, whereas the same strain is less sensitive to the analgesic effect of morphine (Oliverio & Castellano, 1974) than DBA/ZJ (DBA) mice which have less locomotor response. Regional brain differences in the content of dopamine and acetylcholine have been suggested as being responsible for the opposite behavioural effects produced by morphine in the two strains of mice (Ebel, Hermetet & Mandel, 1973; Mandel, Ebel & others, 1973; Kempf, Greilsauer & others, 1974). To avoid the possibility that absorption and metabolism may play a role in determining the different responses to morphine in C 57 and DBA mice we used intracerebroventricular (i.c.v.) administration, to see whether results by this route confirmed those obtained with morphine given intraperitoneally. Moreover, the evidence for the existence in brain of an endogenous ligand with affinity for opiate receptors (Hughes, Smith & others, 1975) followed by the isolation of two pentapeptides methionine-enkephalin and leucine-enkephalin, prompted us to investigate whether the effects of intracerebroventricularly injected morphine could be reproduced by methionine (Met) enkephalin and the more potent DAIa2-Met-enkephalin. Male DBA and C 57 mice (20-24 g) received intracerebroventricular injections as described by Haley & McCormick (1957). I n all the experiments we compared the effects elicited by the opiates in the two inbred strains of mice with those produced by the same drugs in Swiss mice. Morphine hydrochloride, Met-enkephalin and ~-AIa~-Met-enkephalin were dissolved in pyrogen-free water and microinjected in a volume of 10 111. Analgesia was measured by the hot plate method of Eddy, Fuhrmeister Touchberry & Lieberman (1950). The time in seconds from contact with the plate until a hind paw lick or jump occurred was recorded as the response latency. Morphine hydrochloride (0.5 pg/ mouse), Met-enkephalin (50 pglmouse) and D-Alal-Metenkephalin (0.06 pg/mouse) were injected in doses that

Flavia Bruno

Papers

Usage of plant food supplements across six European countries: findings from the PlantLIBRA consumer survey.

Functional interaction between rat substantia nigra and striatum: GABA and dopamine interrelation

Analgesia and motor activity elicited by morphine and enkephalins in two inbred strains of mice

Information sources in biomedical science and medical journalism: methodological approaches and assessment.

Difference in the development of tolerance to morphine and D-ALA2-methionine-enkephalin in C57 BL/6J and DBA/2J mice.