Effects of antipsychotic drugs on latent inhibition: sensitivity and specificity of an animal behavioral model of clinical drug action

Latent inhibition (LI) of a conditioned emotional response (CER) has been proposed as a quantitative measure of selective attention. We have assessed the parallels of the pharmacology of LI in rats with the clinical pharmacology of schizophrenia. Drug and vehicle treated rats were divided into groups and preexposed 20 times to cage illumination as a CS, or not preexposed. All groups were conditioned with 2 CS-footshock pairings. The following day CER, as measured by interruption of drinking in response to CS presentation, was recorded. LI was observed as a decreased CER in preexposed relative to non-preexposed animals. LI was enhanced by haloperidol 0.3 mg/kg after 7 or 14 daily treatments, but not after a single acute dose. Haloperidol doses of 0.3 and 0.03 mg/kg enhanced LI, while doses of 0.003 and 3.0 mg/kg had no effect. Haloperidol enhancement of LI was unaffected by the coadministration of the anticholinergic agent trihexyphenidyl. Enhancement of LI is exhibited by the antipsychotic drugs fluphenazine, chlorpromazine, thiothixene, thioridazine, mesoridazine, and metoclopramide but not clozapine. The non-antipsychotic drugs pentobarbital, imipramine, chlordiazepoxide, trihexyphenidyl, and promethazine failed to enhance LI. LI exhibits striking parallels to the clinical pharmacology of schizophrenia.Preliminary data were presented in part at the Society for Neuroscience Annual Meeting, Phoenix, AZ, 1989     

五种螯合剂对大鼠体内微量元素影响的观察

观察了５种常用螯合剂对大鼠体内微量元素排出量、组织分布的变化。结果表明，５种螯合剂可不同程度地增加机体必需微量元素Ｚｎ、Ｃｕ、Ｍｇ和Ｃａ经尿液排出量。ＥＤＴＡ和ＤＴＰＡ的影响尤为明显。ＥＤＴＡ和ＤＴＰＡ可使Ｚｎ经尿液的排出量增加１６－５２倍，ＤＴＰＡ使肝脏Ｚｎ含量减少１５．９％（Ｐ〈０．０５），肝脏Ｃｕ含量下降６０％（Ｐ〈０．０５）。ＥＤＴＡ和ＤＴＰＡ注射后，肾中Ｚｎ含量明显增高，相当对照大鼠３．     

吡那地尔对高血压心脏结构和功能重构的影响

在等降压剂量下吡那地尔和赖诺普利可使４月龄自发性高血压大鼠的血压下降６．０￣８．０ｋＰａ，并接近同种属正常血压大刀瓣血压水平。     

An open label trial of raclopride in acute schizophrenia. Confirmation of D2-dopamine receptor occupancy by PET

Raclopride, a highly selective D2-dopamine receptor antagonist, was administered in doses up to 4 mg b.i.d. to ten schizophrenic patients in an open label non-comparative study lasting 4 weeks. Safety, tolerability, potential antipsychotic effect, prolactin response and drug effect on plasma homovanillic acid were evaluated. Central D2-dopamine receptor occupancy was determined by positron emission tomography (PET). No major deviations were found in biochemical and physiological safety parameters. Raclopride was well tolerated. The mean BPRS score was reduced by 55% at endpoint. In the global evaluation seven patients were very much or much improved. Extrapyramidal side effects were recorded in four patients and disappeared after dose reduction or single doses of biperiden. An increase in plasma prolactin of short duration was observed in both sexes. A significant decrease of plasma HVA was obtained after 4 weeks of treatment. In two of the patients the central D2-dopamine receptors occupancy was measured using PET. The receptor occupancy was 68 and 72% which is the same as that found in patients treated with conventional neuroleptics.     

Dose-response curves of homovanillic acid in pre-frontal cortex and caudate following antipsychotic drugs: relation to clinical potencies

Dose-response curves for the elevation of homovanillic acid (HVA) levels, determined by high performance liquid chromatography using electrochemical detection, in the pre-frontal cortex and caudate of rats after acute treatment with 12 antipsychotic drugs are presented. The order of potency in both brain regions was: haloperidol fluphenazine > loxapine > trifluoperazine > thiothixene > molindone > clopenthixol > chlorpromazine > metoclopramide > thioridazine > clozapine > sulpiride. This ranking is roughly correlated with that based on clinical potencies. The relative elevation of the content of HVA was weaker in the pre-frontal cortex than in the caudate for all drugs tested, except clozapine at a high dose.     

Autonomic control of acid phosphatase exocrine secretion by the rat prostate

Summary In vivo prostatic secretion was collected from retired breeder Sprague Dawley rats using a method for isolated perfusion of the rat prostatic urethra. Enzymatic acid phosphatase determination was performed on the collected effluent. Control acid phosphatase secretion was 24.2±2.7 nm over 30 minutes. Intravenous phenylephrine 5 mg/kg stimulated a 10 fold increase in acid phosphatase secretion. The secretion seen with phenylephrine was dose dependent and could be blocked with prazosin, but not yohimbine, atropine, or propranolol. Intravenous -adrenergic agonist isoproterenol caused no increase in the secretion of rat prostatic acid phosphatese. Intravenous administration of the cholinergic agonist pilocarpine also resulted in a dose dependent rise in acid phosphatase secretion. The stimulation seen could be blocked by atropine but not phentolamine or propranolol. The stimulation of acid phosphatase secretion seen with ₁ adrenergic or cholinergic agonists was not additive. Intravenous vasoactive intestinal peptide did not stimulate acid phosphatase secretion nor did it augment the secretion induced by ₁ adrenergic or cholinergic agonists. Release of acid phosphatase into rat prostatic exocrine secretion is under both ₁ adrenergic and cholinergic control.Supported by the US Veterans Administration     

Clinical applications of colour Doppler energy imaging in the female reproductive tract and pregnancy

This review describes the usefulness of colour Doppler energy (CDE) (or power Doppler) imaging to measure vascularization in the female reproductive tract. CDE imaging is characterized by an increased sensitivity to flow, and thus may be useful in low-flow states and when optimal Doppler angles cannot be obtained. In addition, longer segments of vessels and more individual vessels can be visualized with CDE imaging. The role of CDE imaging in the evaluation of stromal vasculature in normal and in polycystic ovaries is described, and the relationship between follicular vascularity and outcome following in-vitro fertilization are discussed, together with the findings obtained from the evaluation of thecal arteriole of corpus luteum in early pregnancy. The fundamental role of CDE imaging in differentiation among ovarian masses is also reviewed. We summarize the role of CDE imaging in pregnancy, and describe two new applications of three-dimensional power Doppler sonography and the use of ultrasound contrast media. In conclusion, CDE imaging can replace conventional colour Doppler when the information on the direction of flow is not useful. Moreover, the technique appears superior to others for describing microvascular architecture and determining the presence or absence of flow.     

Evaluation of the Chemical Composition of Dacryodes Edulis and Raphia Hookeri Mann and Wendl Exudates used in Herbal Medicine in South Eastern Nigeria

The phytochemical contents and medicinal values of Dacroydes edulis and Raphia hookeri exudates were investigated. Phytochemical screening of the plant showed that they contain the presence of bioactive compounds comprising saponins (2.08–3.98mg 100g⁻¹), alkaloids (0.28–0.49 mg 100g⁻¹), tannins (0.47–0.72 mg 100g⁻¹), flavonoids (0.26–0.39 mg 100g⁻¹), and phenolic compounds (0.01–0.05 mg 100g⁻¹). The carbohydrates, lipids and protein content were 77.42–78.90%, 2.02–4.185% and 16.63–18.38% respectively. The exudates are a good source of water soluble vitamins; ascorbic acid (7.04–26.40 mg 100g⁻¹), niacin (3.12–4.00 mg 100g⁻¹), riboflavin (0.14–0.54 mg 100g⁻¹) and thiamine (0.15–0.22 mg 100g⁻¹),). Both plants exudates are good sources of minerals such as Ca, Mg, P, Fe, Zn, Cu and Mn while Cr and Co were trace. These results indicate that exudates can be potential sources of feedstock for the pharmaceutical industry.     

Central nervous system inflammatory response after cerebral infarction as detected by magnetic resonance imaging

Brain inflammation contributes to the tissue injury caused by ischemic stroke. Macrophages as the most abundant inflammatory cell population in stroke lesions can be visualized using ultrasmall superparamagnetic iron oxide (USPIO) as a cell-specific contrast agent for magnetic resonance imaging (MRI). The aim of our present study was to delineate the inflammatory response during experimental cerebral infarction by means of USPIO-enhanced MRI and to correlate the spatial distribution of USPIO-induced MR signal alterations with cellular infiltration and iron deposition. To this end USPIOs were administered to Wistar rats 5 days after photothrombotic cerebral infarction. MR imaging at 7 T performed 24 h later displayed a rim-like signal loss around the infarction in the USPIO treated animals. On histological brain sections obtained from the same animals after MRI the distribution of iron and ED1+ phagocytes was in full spatial agreement with the signal loss seen on T2*-weighted images. Our study validates USPIO-enhanced MRI as an important tool for the noninvasive visualization of brain inflammation in stroke and other CNS pathologies.