Implications of new legislation (US FSMA) and guidelines (EC) on the establishment of management systems for agricultural water.

This report summarizes key messages related to agricultural water quality as discussed by an ad hoc panel at the 1st International Symposium of Food Safety in Santiago, Chile. Participating representatives of the academia, industry and government of diverse geographical backgrounds and the audience discussed topics such as (1) implications of the US Food Safety Modernization Act (FSMA: www.fda.gov/Food/GuidanceRegulation/FSMA/ucm277706.htm) on the Agricultural Water Quality, (2) comparisons between MPN and CFU in analyzing water quality, (3) alternatives to fecal indicator bacteria (FIB) to be used as indicators to evaluate water quality, and (4) vegetative buffers as an alternative to reduce pathogen loads in agricultural surface waters. Panelists identified the following key messages for each topic discussed that are related to agricultural water quality: (1) the FSMA regulation and the new guidance document elaborated by the EC are highly relevant as they provide a definition of agricultural water and specific criteria for different water uses and circumstances; (2) FSMA supports modification from MPN to CFU; (3) Growers require more alternatives for treatment of agricultural water; (4) Vegetative buffers are a potential practical and feasible alternative for agriculture producers to reduce the pathogen and fecal pollution loads of in their agricultural waters.

Comparison of human and southern sea otter (Enhydra lutris nereis) health risks for infection with protozoa in nearshore waters.

Cryptosporidium and Giardia spp. are waterborne, fecally-transmitted pathogens that cause economic loss due to gastroenteritis and beach closures. We applied quantitative microbial risk assessment (QMRA) to determine the health risks for humans and sea otters due to waterborne exposure of Cryptosporidium and Giardia spp. when swimming in three types of surface waters: river, stormwater and wastewater effluent during the wet and dry seasons in the central coast of California. This is the first application of QMRA to estimate both the probability of infection in Southern sea otters and the probability of illness in humans, using microbial source tracking (MST) as a variable. Children swimming close to stormwater discharges had an estimated Cryptosporidium-associated illness probability that exceeded the accepted U.S. EPA criteria (32 illnesses/1000 swimmers or 3.2%). Based on the assumption that sea otters are as susceptible as humans to Cryptosporidium infection, the infection probabilities were close to 2% and 16% when sea otters were swimming at the end of points of rivers and stormwater discharges, respectively. In the case of Giardia, infection probabilities of 11% and 23% were estimated for sea otters swimming at the end of point of wastewater discharges, assuming that sea otters are as susceptible as gerbils and humans, respectively. The results of this QMRA suggest that 1) humans and sea otters are at risk when swimming at outflow sites for rivers, stormwater and treated wastewater effluent; 2) reduced loads of viable protozoan cysts and oocysts in recreational water can lessen the probability of infection of humans and sea otters; and 3) the risk of infection of humans and sea otters can be reduced with the treatment of wastewater to decrease oocyst and cyst viability before effluent is released into the sea.

Molecular epidemiology of Cryptosporidium spp. and Giardia spp. in mussels (Mytilus californianus) and California sea lions (Zalophus californianus) from Central California.

Cryptosporidium and Giardia are of public health importance, with recognized transmission through recreational waters. Therefore, both can contaminate marine waters and shellfish, with potential to infect marine mammals in nearshore ecosystems. A 2-year study was conducted to evaluate the presence of Cryptosporidium and Giardia in mussels located at two distinct coastal areas in California, namely, (i) land runoff plume sites and (ii) locations near sea lion haul-out sites, as well as in feces of California sea lions (CSL) (Zalophus californianus) by the use of direct fluorescent antibody (DFA) detection methods and PCR with sequence analysis. In this study, 961 individual mussel hemolymph samples, 54 aliquots of pooled mussel tissue, and 303 CSL fecal samples were screened. Giardia duodenalis assemblages B and D were detected in hemolymph from mussels collected near two land runoff plume sites (Santa Rosa Creek and Carmel River), and assemblages C and D were detected in hemolymph from mussels collected near a sea lion haul-out site (White Rock). These results suggest that mussels are being contaminated by protozoa carried in terrestrial runoff and/or shed in the feces of CSL. Furthermore, low numbers of oocysts and cysts morphologically similar to Cryptosporidium and Giardia, respectively, were detected in CSL fecal samples, suggesting that CSL could be a source and a host of protozoan parasites in coastal environments. The results of this study showed that Cryptosporidium and Giardia spp. from the feces of terrestrial animals and CSL can contaminate mussels and coastal environments.

Individual subject meta-analysis of parameters for Giardia duodenalis shedding in animal experimental models.

Giardia duodenalis is a zoonotic protozoan parasite with public health importance worldwide. While articles about animal model infectivity have been published for G. duodenalis, the studies have used diverse protocols and parameters to evaluate the infectivity of this protozoan parasite. Hence, the objectives of this study were to (1) conduct a meta-analysis of published literature for cyst shedding and diarrhea outcomes in animal models and (2) develop recommendations to help standardize experimental dose response studies. Results showed that, for the outcome of cyst shedding in faeces, the covariates of infective stage (cyst versus trophozoite), Giardia dose, and the interactions between doses and infective stage, as well as dose and species of experimental host, were all significant (P value ≤ 0.05). This study suggests inoculation of the experimental host with cysts rather than trophozoites and administration of higher doses of Giardia will most likely result in cyst shedding. Based on the results of this meta-analysis, the infective stage (cyst versus trophozoite), parasite dose, and the interactions between dose and infective stage, as well as dose and species of experimental host, should be considered when designing experimental dose response studies that will assist in the study of zoonotic neglected tropical diseases globally.

Individual subject meta-analysis of parameters for Cryptosporidium parvum shedding and diarrhoea in animal experimental models.

Cryptosporidium is a zoonotic protozoan parasite with public health importance worldwide. The objectives of this study were to (1) conduct a meta-analysis of published literature for oocyst shedding and diarrhoea outcomes, and (2) develop recommendations for standardization of experimental dose-response studies. Results showed that for the outcome of oocyst shedding in faeces, the covariates 'experimental species', 'immunosuppression', 'oocyst dose' and 'oocyst dose' × 'age' were all significant (P≤0.05). This study suggests that exposing mice, piglets, or ruminants, and using immunosuppressed experimental hosts, is more likely to result in oocyst shedding. For the outcome of diarrhoea in experimentally infected animal species, the key covariates 'experimental species', 'age' and 'immunosuppression' were significant (P≤0.2). Therefore, based on the results of this meta-analysis, these variables should be carefully reported and considered when designing experimental dose-response studies. Additionally, detection of possible publication bias highlights the need to publish additional studies that convey statistically non-significant as well as significant results in the future.

[Information strategies in a polyvalent Intensive Care Unit]. / Estrategias de información en una Unidad de Cuidados Intensivos polivalente.

INTRODUCTION: Understanding the information provided to families and surrogates of the critically ill patients admitted to ICUs and its adequate communication without contradictions, is a fundamental aspect related with the possible participation of these persons in the treatment decision making and with the quality perceived regarding the care process. Our aim in this study is to assess these two aspects (information and communication of information). DESIGN: Opinion study elaborated by the medical team and nursing staff of a multidisciplinary ICU. METHOD: Observational qualitative study performed through an open answers questionnaire. Search for agreement on terminology and concepts that should be included in the information and estimation of the different contents of information provided by the main health care professional groups (physicians and nurses). Using the Delphi technique to elaborate an information communication sheet between different staff members in order to homogenize the information process. RESULTS: The analysis of the questionnaire reveals the great heterogeneity of the contents and modes of information provided. This may cause difficulties in understanding and the integration of families and relatives in the care process. The agreement achieved among the different between physicians to facilitate the information and avoid subjective interpretations by the informed people is presented.

Expression of GDNF transgene in astrocytes improves cognitive deficits in aged rats.

Glial cell line-derived neurotrophic factor (GDNF) was assayed for its neurotrophic effects against the neuronal atrophy that causes cognitive deficits in old age. Aged Fisher 344 rats with impairment in the Morris water maze received intrahippocampal injections at the dorsal CA1 area of either a lentiviral vector encoding human GDNF or the same vector encoding human green fluorescent protein as a control. Recombinant lentiviral vectors constructed with human cytomegalovirus promotor and pseudotyped with lyssavirus Mokola glycoprotein specifically transduced the astrocytes in vivo. Astrocyte-secreted GDNF enhanced neuron function as shown by local increases in synthesis of the neurotransmitters acetylcholine, dopamine and serotonin. This neurotrophic effect led to cognitive improvement of the rats as early as 2 weeks after gene transduction. Spatial learning and memory testing showed a significant gain in cognitive abilities due to GDNF exposure, whereas control-transduced rats kept their performance at the chance level. These results confirm the broad spectrum of the neurotrophic action of GDNF and open new gene therapy possibilities for reducing age-related neurodegeneration.

The role of 5-HT1B receptors in the regulation of serotonin cell firing and release in the rat brain.

The release of 5-HT in terminal areas of the rodent brain is regulated by 5-HT1B receptors. Here we examined the role of 5-HT1B receptors in the control of 5-HT output and firing in the dorsal raphe nucleus (DR), median raphe nucleus (MnR) and forebrain of the rat in vivo. The local perfusion (30-300 microM) of the selective 5-HT1B receptor agonist CP-93,129 to freely moving rats decreased 5-HT release in the DR and more markedly in the MnR. Likewise, 300 microM CP-93,129 reduced 5-HT output in substantia nigra pars reticulata, ventral pallidum, lateral habenula and the suprachiasmatic nucleus. The effect of CP-93,129 was prevented by SB-224289, but not by WAY-100635, selective 5-HT1B and 5-HT1A receptor antagonists, respectively. SB-224289 did not alter dialysate 5-HT in any raphe nuclei. The intravenous administration of the brain-penetrant selective 5-HT1B receptor agonist CP-94,253 (0.5-2.0 mg/kg) to anesthetized rats decreased dialysate 5-HT in dorsal hippocampus and globus pallidus, increased it in MnR and left it unaltered in the DR and medial prefrontal cortex. SB-224289, at a dose known to block 5-HT1B autoreceptor-mediated effects (5 mg/kg), did not prevent the effect of CP-94,253 on MnR 5-HT. The intravenous administration of CP-94,253 (0.05-1.6 mg/kg) to anesthetized rats increased the firing rate of MnR, but not DR-5-HT neurons. The local perfusion of CP-94,253 in the MnR showed a biphasic effect, with 5-HT reductions at 0.3-3 microM and increase at 300 microM. These results suggest that 5-HT cell firing and release in midbrain raphe nuclei (particularly in the MnR) are under control of 5-HT1B receptors. The activation of 5-HT1B autoreceptors (possibly located on 5-HT nerve endings and/or varicosities within DR and MnR) reduces 5-HT release. The effects of higher concentrations of 5-HT1B receptor agonists seem more compatible with the activation of 5-HT1B heteroreceptors on inhibitory neurons.

How does pindolol improve antidepressant action?

Since 1994, the beta-adrenoceptor and 5-HT(1A/1B) receptor ligand pindolol has been used to accelerate or enhance the clinical effects of antidepressant drugs, such as the selective 5-HT reuptake inhibitors (SSRIs), that act primarily on 5-HT-containing neurones. Pindolol was initially thought to act by preventing the inhibition of 5-HT release, elicited by SSRIs and other 5-HT-acting drugs, as a result of its ability to antagonize the action of 5-HT at midbrain raphe 5-HT(1A) autoreceptors that control the activity of ascending 5-HT-mediated pathways. However, the partial agonist properties of pindolol at 5-HT(1A) receptors and beta-adrenoceptors suggest that other explanations for its action are also possible. In this article, recent controversial data on the mechanism of action of pindolol, which are crucial for the development of more rapid and efficient antidepressant therapies, will be discussed.

On the Applicability of DLVO Theory to the Prediction of Clay Colloids Stability.

The stability behavior of Na-montmorillonite colloids has been studied by combining the analysis of their surface charge properties and time-resolved dynamic light scattering experiments. The chemical surface model for several types of clays, including montmorillonite, has to take into account the double surface charge contribution due to their permanent structural charge and to their pH-dependent charge, which is developed at the edge sites, therefore, these stability studies were carried out as a function of both ionic strength and pH. DLVO theory is largely applied for the prediction of the stability of many colloidal systems, including the natural ones. This work shows that the stability behavior of Na-montmorillonite colloids cannot be satisfactorily reproduced by DLVO theory, using the surface parameters experimentally obtained. Particularly, this theory is unable to explain their pH-dependent stability behavior caused by the small charge at the edge sites. Based on these results, a literature review of DLVO stability prediction of clay colloids was performed. It confirmed that this theory is not capable of taking into account the double contribution to the total surface charge and, at the same time, pointed out the main uncertainties related to the appropriate use of the input parameters for the calculation as, for example, the Hamaker constant or the surface potential. Copyright 2000 Academic Press.

GABAB-RI receptors in serotonergic neurons: effects of baclofen on 5-HT output in rat brain.

The activation of GABAB receptors hyperpolarizes 5-HT neurons and reduces cell firing. In situ hybridization showed the presence of the GABAB-RI receptor transcript in virtually all 5-HT neurons of the dorsal and median raphe nuclei (DR and MnR, respectively) whereas the GAD transcript was present mainly outside these nuclei. The systemic administration of baclofen increased the in vivo 5-HT release in the DR, MnR and several projection areas. As shown previously in the DR, the application of baclofen in the MnR increased the local 5-HT output. Thus, although 5-HT neurons contain inhibitory GABAB-RI receptors, baclofen increased 5-HT release in some brain areas, likely by a preferential action on terminal GABAB autoreceptors in inhibitory inputs to 5-HT neurons. The scarcity of GAD-expressing cells in the DR and MnR suggests that these inputs originate mainly outside these nuclei.

Role of uptake inhibition and autoreceptor activation in the control of 5-HT release in the frontal cortex and dorsal hippocampus of the rat.

1. Using brain microdialysis, we compared the relative role of 5-hydroxytryptamine (5-HT; serotonin) blockade and somatodendritic 5-HT(1A) and/or terminal 5-HT(1B) autoreceptor activation in the control of 5-HT output. 2. Fluoxetine (10 mg kg(-1) i.p.) doubled the 5-HT output in frontal cortex and dorsal hippocampus. The 5-HT(1A) receptor antagonist WAY 100635, (0.3 mg kg(-1) s.c.) potentiated the effect of fluoxetine only in frontal cortex (to approximately 500 % of baseline). 3. Methiothepin (10 mg kg(-1) s.c.) further enhanced the 5-HT rise induced by fluoxetine+WAY 100635, to 835+/-179% in frontal cortex and 456+/-24% in dorsal hippocampus. Locally applied, methiothepin potentiated the fluoxetine-induced 5-HT rise more in the former area. 4. The selective 5-HT(1B) receptor antagonist SB-224289 (4 mg kg(-1) i.p.) enhanced the effect of fluoxetine (10 mg kg(-1) i.p.) in both areas. As with methiothepin, SB-224289 (4 mg kg(-1) i.p.) further enhanced the 5-HT increase produced by fluoxetine+WAY 100635 more in frontal cortex (613+/-134%) than in dorsal hippocampus (353+/-59%). 5. Locally applied, fluoxetine (10 - 300 microM; EC(50)=28 - 29 microM) and citalopram (1 - 30 microM; EC(50)=1.0 - 1.4 microM) increased the 5-HT output two to three times more in frontal cortex than in dorsal hippocampus. These data suggest that the comparable 5-HT increase produced by systemic fluoxetine in frontal cortex and dorsal hippocampus results from a greater effect of reuptake blockade in frontal cortex that is offset by a greater autoreceptor-mediated inhibition of 5-HT release. As a result, 5-HT autoreceptor antagonists preferentially potentiate the effect of fluoxetine in frontal cortex.

Communication during prosthodontic treatment--dentist, patient, and dental nurse.

PURPOSE: This study described and explored verbal communication during prosthodontic treatment. MATERIALS AND METHODS: Sixty-one patients and 15 dentists participated. Sixty-one prosthetic treatment periods, during which fixed tooth- or implant-supported prostheses were placed, were followed. One visit during each treatment period was audio recorded. The recorded verbal communication was analyzed with the Roter Interaction Analysis System-dental. The inter-rater reliability was 95% to 97% for utterance classification and kappa = 0.71 to 0.78 for categorization definition. RESULTS: There were 43,663 utterances available for analysis. Of those, 59% was dentist communication, 28% was patient communication, and 10% was dental nurse communication. Other persons, e.g., dental technicians, contributed with 3%. The dentist-patient communication contained more task-focused than socioemotional behaviors. Female patients used socioemotional talk to a greater extent than did the male patients. Dentists and patients of different genders communicated more overall, especially male dentists with female patients. The age difference between dentist and patient had no effect on the amount or type of communication. The dental nurse talked slightly more with male patients. CONCLUSION: When different genders met there was more communication, and the talk was more socioemotional when the patient was female.

Regulation of the release of 5-hydroxytryptamine in the median raphe nucleus of the rat by catecholaminergic afferents.

The present study was conducted in order to examine the influence of catecholaminergic afferents on the release of serotonin in the median raphe nucleus in vivo. To this aim, selective dopamine D1 and D2, and alpha1- and alpha2-adrenergic agonists and antagonists were administered locally (1, 10 and 100 microM) through a dialysis probe implanted in the median raphe nucleus of freely moving rats. The D1 and D2 agonists, (+/-)-1-phenyl-2,3,4, 5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF-38393) and quinpirole, respectively, and the D1 and D2 antagonists, R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine (SCH-23390) and raclopride, respectively, did not alter the release of serotonin in the median raphe nucleus. The alpha1-adrenoceptor agonist phenylephrine did not modify the release of serotonin in this nucleus, although an increased release was observed when the more potent alpha1-adrenoceptor agonist cirazoline was used. In contrast, the alpha1-adrenoceptor antagonist prazosin reduced the release of 5-hydroxytryptamine (5-HT) in a concentration-dependent manner. The release of 5-HT was also reduced by the alpha2-adrenoceptor agonist clonidine and increased by the alpha2-adrenoceptor antagonist 2-methoxy-idazoxan (RX821002). These results indicate that the release of serotonin in the median raphe nucleus does not appear to be regulated by dopaminergic afferents through the activation of dopamine D1 or D2 receptors. On the contrary, it is suggested that endogenous noradrenaline exerts a direct tonic stimulatory control on the release of serotonin through alpha1-adrenoceptors, and an indirect tonic inhibitory influence through alpha2-adrenoceptors located probably in noradrenergic nerve terminals within the median raphe nucleus.

A microdialysis study of the in vivo release of 5-HT in the median raphe nucleus of the rat.

The present study has examined several characteristics of the release of 5-HT in the median raphe nucleus in terms of its dependence of nerve impulse, provenance of a vesicular storage fraction as well as the regulatory role played by 5-HT1A receptors. Tetrodotoxin (1 microM) and reserpine (5 mg kg(-1), i.p.) virtually suppressed the output of 5-HT. The administration of EEDQ (10 mg kg(-1), i.p.) did not alter the basal release of 5-HT but abolished the reduction of 5-HT release induced by 8-OH-DPAT (0.1 mg kg(-1), s.c.). The perfusion of 1-100 microM of 8-OH-DPAT or the novel 5-HT1A agonist BAY x 3702 decreased the efflux of 5-HT, whereas the perfusion of the 5-HT1A antagonist WAY-100635 failed to alter 5-HT release. The decrease in dialysate 5-HT induced by 100 microM 8-OH-DPAT was reversed by the concurrent perfusion of 100 microM WAY-100635. Also, the perfusion of 100 microM WAY-100635 for 2 h inhibited partly the reduction of 5-HT release evoked by the systemic administration of 8-OH-DPAT (0.1 mg kg(-1)). These results indicate that extracellular 5-HT in the median raphe nucleus is stored in vesicles and released in an impulse-dependent manner. Also, the basal release of 5-HT in the median raphe nucleus does not appear to be under the tonic control of somatodendritic 5-HT1A receptors by endogenous 5-HT. Instead, this feedback mechanism seems to be triggered when an excess of the transmitter or a 5-HT1A agonist is present in the extracellular space of the median raphe nucleus.

Simultaneous comparison of cerebral dialysis and push-pull perfusion in the brain of rats: a critical review.

Over the last 30 years, studies of the in vivo activity of neurotransmitters and other endogenous factors in the brain have comprised a major effort in the neurosciences. Historically, the technology of push-pull perfusion was utilized as a major approach to investigations in this field. In the last 10 years, cerebral dialysis has been used as an alternative method essentially for the same scientific purpose, since the perfusion technique was viewed as difficult and excessively damaging to tissue. This review considers the representative literature in which both systems have been used to study local neurochemical responses to a drug or other chemical factor, a physiological condition or other situation. In addition, new experiments have been undertaken to compare, in the same animal and at the same time, the utility and properties inherent in the techniques of push-pull perfusion and cerebral dialysis in terms of the profile of a neurotransmitter activity and their local histopathological effects. A miniaturized 33/26 ga push-pull needle and a 24 ga dialysis probe were implanted simultaneously in the left and right caudate nuclei, respectively, in the anesthetized rat. An artificial cerebrospinal fluid (CSF) was perfused simultaneously through both devices at a rate of 10 microliters/min in the push-pull cannula and at 1.0 or 2.0 microliters/min in the dialysis probe. Within a series of 8-10 successive perfusions, excess K+ ions in a concentration of either 30 or 60 mM were incorporated in the CSF and delivered simultaneously to both the push-pull cannula and dialysis probe. Samples of perfusate and dialysate were assayed chromatographically by coulometric HPLC detector and quantitated in terms of the pg/min efflux of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). The results showed that the resting level of DA was almost undetectable in dialysate samples from either structure; in push-pull perfusates the recovery of DA ranged between 7.0 to 10.0 pg/min, which was increased threefold by excess K+ ions. The recovery of DA and the three metabolites in samples of push-pull perfusate was two to four times that in samples of dialysate during the condition of excess K+ ions. Post-mortem histological analysis of the sites of perfusion and dialysis revealed little or no differences in the cytological damage induced by either the perfusion needle or dialysis probe. Finally, the advantages and limitations of each of these two experimental approaches to in vivo analysis of neurotransmitter efflux are reviewed in relation to the selection of an open or closed system for the on-line study of in vivo neurochemical events.

Gas chromatography study of the adsorption of refrigerating fluids on microporous solid adsorbents.

Adsorption isotherms for microporous solids have been determined by elution gas chromatography. Adsorbents are of ;molecular sieves' type; their utilization in affinity thermal machines is envisaged. These machines work in a relatively high domain of pressure for the adsorbate, so the chromatographic technique is generally inadequate for their study. The possibility of increasing the maximal pressures reached by chromatography has been investigated in relation with: the carrier gas flow rate, the length and width of columns, the injected adsorbate mass. This study has been made for different solid adsorbents (zeolite 4A and 13X, silica gel), in different shapes (small stick, pellet, powder), and with different adsorbates (water, methanol, ethanol). In the most favorable conditions that have been derived, the qualities of the chromatographic method, rapidity, simplicity and large range of measures, appear well fitted to the search of this kind of isotherms which does not require a great accuracy.

Comparative study in the rat of the actions of different types of stress on the release of 5-HT in raphe nuclei and forebrain areas.

The effects of several stress procedures on the release of 5-HT in the dorsal and median raphe nuclei (DRN and MRN, respectively) and in forebrain structures of the rat brain innervated by both nuclei have been studied using intracerebral microdialysis. Handling for 30 sec, a saline injection and forced swimming for 5 min elevated significantly the 5-HT output in the MRN. The 5-HT output in the DRN was also enhanced by a saline injection. With regard to the forebrain structure examined, handling and forced swimming increased dialysate 5-HT in the amygdala. The injection of saline induced a slight, but significant, elevation of 5-HT in the medial prefrontal cortex. In contrast, the outflow of 5-HT was significantly reduced in the ventral hippocampus and medial prefrontal cortex following forced swimming and this effect persisted well beyond the cessation of the swim session. These results indicate that the efflux of 5-HT in the MRN appears to respond to different forms of stress, whereas that in the DRN only increases after the injection of saline. The release of 5-HT in the forebrain structures is also dependent on the type of stress procedure and the region studied.

Lesioning of midbrain raphe nuclei with 5,7-DHT fails to alter ethanol intake in the low alcohol drinking (LAD) rat.

1. The effect of 10 g 5,7-dihydroxytryptamine (5,7-DHT) micro-injected into both the dorsal (DRN) and the median raphe nuclei (MRN) on the intake of ethanol in the low alcohol drinking (LAD) rat was measured using a standard 3-30% ethanol preference test. 2. The combined lesion of both midbrain structures depleted the levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) significantly in each of eight major regions of the brain. The levels of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) remained unchanged after the lesion. 3. The effects of the neurotoxin lesions on the intakes of ethanol, food, water and total amount of fluid consumed were not significant. 4. The results corroborate our previous findings with the Sprague-Dawley strain of rat and suggest that although brain 5-HT may play a role in the maintenance of basal patterns of ethanol drinking, this monoamine may not be able to modify further the consumption of this fluid after lesioning with 5,7-DHT.

Action of harman (1-methyl-beta-carboline) on the brain: body temperature and in vivo efflux of 5-HT from hippocampus of the rat.

Harman (1-methyl-beta-carboline) has been shown previously to act on the hippocampus of the rat in terms of its evocation of anxiogenic responses and induction of alcohol preference. In the present experiments, the localized perfusion of 200 microM harman in the dorsal hippocampus of freely moving rats increased the levels of serotonin (5-HT) but not 5-hydroxyindoleacetic acid (5-HIAA) in cerebral dialysates. The systemic administration of 5.0-20 mg/kg harman also enhanced 5-HT in the perfusates but reduced the levels of 5-HIAA in a dose-dependent manner, probably as a result of the inhibition of the enzyme monoamine oxidase type A (MAO-A). Harman given systemically in doses of 2.5-20 mg/kg induced an intense hypothermia, with a maximum fall produced by the 5.0 mg/kg dose. This fall in body temperature (Tb) induced by 5.0 mg/kg harman was not antagonized by 5.0 mg/kg of (+/-)-pindolol. Further, pretreatment of the rats with parachlorophenylalanine (pCPA) also failed to alter the harman-induced hypothermia. The systemic administration of 10 mg/kg of the MAO-A inhibitor, clorgyline, also lowered Tb significantly. Overall, the present experiments show that harman apparently influences 5-HT systems in the brain by its action in inhibiting MAO-A. This property is likely responsible also for the harman-induced increase of 5-HT in the hippocampus of the rats.