Assessing the benefits and usefulness of Schwartz Centre rounds in second-year medical students using clinical educator-facilitated group work session: not just "a facilitated moan"!

BACKGROUND: An experiential curriculum exposing medical students to the clinic early has many benefits but comes with the emotional stress this environment engenders. Schwartz rounds (SR) are an effective means to combat emotional stress and increasingly used in UK and USA hospitals. Recent studies show that the SR format may also provide benefits for medical students. This study aimed to investigate whether the guidance of SR in second year medical students provides the same benefits as to healthcare professionals. METHODS: SR assessment involved 83 s year MBChB students in facilitated groupwork sessions. Topics discussed were "change and resilience" and "duty of candour". Students completed a Likert Scale questionnaire evaluating outcomes proffered by the Point of Care Foundation in collaboration with the Schwartz Foundation, with freeform feedback. RESULTS: There was an 86% completion rate with 25% providing written feedback. Participants were more likely to agree than disagree that SR were beneficial. SR effectiveness in enhancing students' working relationship awareness and skills was strongly correlated with understanding the purpose of, and engagement with, the SR (P < 0.001). Similarly, engagement with the SR was strongly correlated with self-reporting of enhanced patient-centredness (P < 0.001). Freeform feedback could be grouped into five themes that revolved around understanding of the SR and engagement with the process. Many positive comments regarded the SR as a forum not only to "learn experientially" but to so in a "safe environment". Many negative comments stemmed from students not seeing any benefits of engagement with the SR, in that sharing experiences was "unbeneficial", "empathy is inherent and not learnt", or that sharing emotional problems is simply "moaning". CONCLUSION: SRs are an effective way of fostering empathy and understanding towards patients and colleagues. However, for the students to benefit fully from the SR it is necessary for them to engage and understand the process. Therefore, for the successful implementation of SR into pre-clinical medical education, it is important to help students realise that SR are not merely a "facilitated whinge".

Cross-cultural adaptation and validation of a quality of life questionnaire: the Nasal Obstruction Symptom Evaluation questionnaire.

BACKGROUND: The Nasal Obstruction Symptom Evaluation (NOSE) instrument is a disease-specific questionnaire for assessing the outcome of an intervention in nasal obstruction in trials. This instrument is only available in the English language and cross-culturally valid questionnaires are very important for all research, including nasal obstruction. The aim of the current study was to reproduce the cross-cultural adaptation process for the NOSE questionnaire in the Portuguese language (NOSE-p). METHODOLOGY/PRINCIPAL: Cross-cultural adaptation and validation of the instrument were divided into two stages. Stage 1 involved four bilingual professionals, an expert committee and the author of the original instrument. In Stage 2, the NOSE-p was tested on 33 patients undergoing septoplasty for internal consistency, test-retest reliability, construct validity, discriminant validity, criterion validity, and response sensitivity. RESULTS: The cross-cultural adaptation process was completed and the NOSE-p was demonstrated to be a valid instrument with satisfactory construct validity. It showed an adequate internal consistency reliability and adequate test-retest reliability. It could discriminate between patients with and without nasal obstruction and it has a high response sensitivity to change. CONCLUSIONS: The cross-cultural adaptation and validation process demonstrated to be valid and the NOSE-p proved to be applicable in Brazil.

Frequency of sinus disease in normal subjects and patients with benign paroxysmal positional vertigo.

BACKGROUND/AIMS: To determine if patients with benign paroxysmal positional vertigo (BPPV) have a higher frequency of rhinosinusitis than people with normal vestibular function. METHODS: The subjects were 52 patients with BPPV and 46 normal people. Every subject had a sinus CT scan, a blood draw for IgE and a rhinologic examination by an otolaryngologist. RESULTS: The frequency of rhinosinusitis based on physician diagnosis was 49% and based on CT scan findings 59%. This difference approached significance (p = 0.08). The observed frequency of rhinosinusitis was higher than predicted by survey data about the southern US region. The data trended toward higher prevalence of rhinosinusitis (by physician diagnosis) in the BPPV patients versus controls (58 vs. 39%, p = 0.06). CONCLUSION: BPPV patients have a higher frequency of sinus disease compared to people with normal vestibular systems, perhaps due to age differences, but physiologic factors may also be involved. The higher frequency of rhinosinusitis in this geographical area than reported rates based on survey data raises concerns about the usefulness of questionnaire data for estimating population prevalence.

Identification and management of undiagnosed and undertreated allergic rhinitis in adults and children.

Allergic rhinitis (AR) is a common health problem that affects adults, adolescents and children and is often undiagnosed or inadequately treated. Because AR is not a life-threatening disease, many patients do not seek medical treatment for their symptoms, and others self-medicate with over-the-counter medications, often sedating antihistamines. However, untreated or inadequately treated AR can substantially impair overall quality of life (QOL) by causing fatigue, headache, cognitive impairment and other problems. The risk for comorbid conditions, such as asthma, otitis media, and lymphoid hypertrophy with obstructive sleep apnea, can increase, and the symptoms of AR can worsen if AR is not adequately treated. Among the symptoms of AR, nasal congestion has been described by patients as the most bothersome because it disrupts sleep, resulting in diminished daytime performance. A new congestion screening tool, the Congestion Quantifier, has been developed to aid in the diagnosis and treatment of AR and to help guide treatment decisions. Intranasal corticosteroids (INSs) are recommended as effective pharmaceutical treatments for controlling the symptoms of AR. Randomized, controlled trials in children and adults have demonstrated that INSs relieve rhinitis symptoms, thereby improving QOL in individuals with seasonal or perennial AR. Most INSs are approved for use in children >or=6 years of age, but mometasone furoate and fluticasone furoate are approved for use in children as young as 2 years of age and fluticasone propionate for children >or=4 years old. Long-term benefits have also been seen with the use of immunotherapy, although some patients, especially children, resist the injections used in subcutaneous immunotherapy. Recent studies with sublingual immunotherapy have indicated that it might be an effective and well-tolerated alternative to immunotherapy injections.

Dendritic colocalisation of serotonin1B receptors and the glutamate NMDA receptor subunit NR1 within the hippocampal dentate gyrus: an ultrastructural study.

The serotonin1B receptor (5-HT1BR) plays a significant role in cognitive processing, which also involves glutamatergic transmission via N-methyl-D-aspartate (NMDA) receptors. It is implicated in a range of disorders, many of which also have a cognitive component, and therefore represents a valuable therapeutic target. 5-HT1BRs are described as predominantly pre-synaptic auto- and/or hetero-receptors, modulating the release of neurotransmitters including glutamate. However, a detailed assessment of localisation within the hippocampus, a pivotal structure in cognitive processing, has been absent. Here, we have conducted an electron microscopic examination of the subcellular distribution of the 5-HT1BR, NMDA receptor subunit NR1 and neurotransmitter gamma-aminobutyric acid (GABA), within the hippocampal dentate gyrus. Ultrastructurally, 18% of 5-HT1BR immunoreactivity was pre-synaptic (within axons and axon terminals), and 65% post-synaptic (within dendrites and dendritic spines); no significant differences were found between molecular layer subdivisions. Post-synaptic labelling was cytoplasmic and membranous. Spinous labelling was more frequently bound to the plasma membrane, but not usually directly associated with the synaptic specialisation. Only 16% of 5-HT1BR positive profiles displayed NR1 labelling, of which most were dendrites, at a slightly higher level within the inner, compared to middle and outer molecular layer divisions. 5-HT1BR labelled profiles rarely showed labelling for GABA. These findings indicate that within the dentate gyrus, pre-synaptic 5-HT1BRs may modulate non-GABAergic neurotransmitter release whilst post-synaptic 5-HT1BRs are expressed on segments of mainly NR1 negative granule cell processes. However, a subpopulation of 5-HT1BRs is expressed on NR1 positive dendrites. Here, the 5-HT1BR may be an interesting target for modulation of NMDA receptor mediated currents.

Reversible reduction in dendritic spines in CA1 of rat and ground squirrel subjected to hypothermia-normothermia in vivo: A three-dimensional electron microscope study.

A study was made at electron microscope level of changes in the three-dimensional (3-D) morphology of dendritic spines and postsynaptic densities (PSDs) in CA1 of the hippocampus in ground squirrels, taken either at low temperature during hibernation (brain temperature 2-4 degrees C), or after warming and recovery to the normothermic state (34 degrees C). In addition, the morphology of PSDs and spines was measured in a non-hibernating mammal, rat, subjected to cooling at 2 degrees C at which time core rectal temperature was 15 degrees C, and then after warming to normothermic conditions. Significant differences were found in the proportion of thin and stubby spines, and shaft synapses in CA1 for rats and ground squirrels for normothermia compared with cooling or hibernation. Hypothermia induced a decrease in the proportion of thin spines, and an increase in stubby and shaft spines, but no change in the proportion of mushroom spines. The changes in redistribution of these three categories of spines in ground squirrel are more prominent than in rat. There were no significant differences in synapse density determined for ground squirrels or rats at normal compared with low temperature. Measurement of spine and PSD volume (for mushroom and thin spines) also showed no significant differences between the two functional states in either rats or ground squirrels, nor were there any differences in distances between neighboring synapses. Spinules on dendritic shafts were notable qualitatively during hibernation, but absent in normothermia. These data show that hypothermia results in morphological changes which are essentially similar in both a hibernating and a non-hibernating animal.

On a possible early identification procedure for babies at high risk for autistic spectrum disorder.

A hypothesis for a method that may make possible the early identification of neonates at high risk for later development of autistic spectrum disorder (ASD) is set forth. The method is a test of the assertion that unusually high testosterone concentrations in amniotic fluid (TECAFs) are predictive of later ASD diagnoses. The statistical distribution of TECAFS, obtained in the 14-20th week of pregnancy, is used to determine the critical TECAF value above which the highest 2% lie and thus identify the babies at high risk for later ASD syndromes. From presently available data a single numerical value cannot be obtained. However, a critical value calculated from the mean TECAF value of a group of gender identified amniotic fluid samples, which are all assayed by the same technique, and multiples of the standard deviation (SD) of the TECAFs of that group, leads to an estimate of the critical TECAF value. We estimate that this critical value is equal to the mean plus 2.6 times the standard deviation, (m+2.6 SD), of the set of measurements. A rough calculation of the number of neonates that would be needed for a test of this method is discussed.

FENS 2000 - Federation of European Neuroscience Societies millennium meeting.

In two articles by Wolf Singer, published in TINS in 1994 and 1997, brief analyses were presented of the problems faced by the European neuroscience community in its attempt to provide a cohesive response to meet the challenge of the proclamation of the 'Decade of the Brain'. One of the most-important decisions was to promote a forum for European neuroscience that, among other activities, would hold bi-annual meetings, alternating with meetings of partner European neuroscience societies in the intervening year. The first fruit of this was the enormously successful meeting held in Berlin in June 1998. The next meeting, the FENS millennium meeting, will be held in Brighton, UK (24-28 June 2000).

Hippocampal synapses: do they talk to their neighbours?

Recent experimental findings show that fast synaptic transmission can extend its actions beyond the immediate synaptic cleft. Whether this phenomenon results in significant crosstalk between typical neighbouring synapses remains unclear. This article considers two areas of the hippocampus, the CA1 and dentate gyrus, where important neural processing occurs. The results discussed do not provide a simple answer to the question of whether synapses can 'talk' to their neighbours, but they do reveal crucial physiological constraints that determine the significance of synaptic crosstalk, thus adding considerably to our understanding of chemical synaptic transmission.

Chronic restraint stress induces changes in synapse morphology in stratum lacunosum-moleculare CA1 rat hippocampus: a stereological and three-dimensional ultrastructural study.

Chronic restraint stress is known to affect the morphology and synaptic organization of the hippocampus, predominantly within CA3 but also in CA1 and dentate gyrus. In this study, we provide the first evidence for specific ultrastructural alterations affecting asymmetric axo-spinous synapses in CA1 stratum lacunosum-moleculare following chronic restraint stress (6 h/day, 21 days) in the rat. The structure of asymmetric axo-spinous post-synaptic densities was investigated using serial section three-dimensional reconstruction procedures in control (n=4) and chronic restraint stress (n=3) animals. Dendritic spine profiles (spine head+neck) associated with the sampled synaptic contacts (30 per animal) were also reconstructed in three-dimensions. Morphometric analyses revealed a significant increase in post-synaptic density surface area (+36%; P=0.03) and a highly significant increase in post-synaptic density volume (+79%; P=0.003) in the chronic restraint stress group. These changes were directly associated with 'non-macular' (perforated, complex and segmented) post-synaptic densities. A highly significant overall increase in the 'post-synaptic density surface area/spine surface area' ratio was also detected in the chronic restraint stress group (+27%; P=0.002). In contrast, no quantitative changes in spine parameters were found between groups. The Cavalieri method was used to assess the effects of chronic restraint stress exposure upon CA1 hippocampal volume. The mean volume of total dorsal anterior CA1 hippocampus was significantly lower in the chronic restraint stress group (-16%; P=0.036). However, when corrected for volume changes, no significant alteration in a relative estimate of the mean number of asymmetric axo-spinous synapses was detected in CA1 stratum lacunosum-moleculare between control and chronic restraint stress groups. The data indicate a structural remodeling of excitatory axo-spinous synaptic connectivity in rat CA1 stratum lacunosum-moleculare as a result of chronic restraint stress.

Ultrastructural distribution of the alpha7 nicotinic acetylcholine receptor subunit in rat hippocampus.

Acetylcholine (ACh) is an important neurotransmitter in the mammalian brain; it is implicated in arousal, learning, and other cognitive functions. Recent studies indicate that nicotinic receptors contribute to these cholinergic effects, in addition to the established role of muscarinic receptors. In the hippocampus, where cholinergic involvement in learning and memory is particularly well documented, alpha7 nicotinic acetylcholine receptor subunits (alpha7 nAChRs) are highly expressed, but their precise ultrastructural localization has not been determined. Here, we describe the results of immunogold labeling of serial ultrathin sections through stratum radiatum of area CA1 in the rat. Using both anti-alpha7 nAChR immunolabeling and alpha-bungarotoxin binding, we find that alpha7 nAChRs are present at nearly all synapses in CA1 stratum radiatum, with immunolabeling present at both presynaptic and postsynaptic elements. Morphological considerations and double immunolabeling indicate that GABAergic as well as glutamatergic synapses bear alpha7 nAChRs, at densities approaching those observed for glutamate receptors in CA1 stratum radiatum. Postsynaptically, alpha7 nAChRs often are distributed at dendritic spines in a perisynaptic annulus. In the postsynaptic cytoplasm, immunolabeling is associated with spine apparatus and other membranous structures, suggesting that alpha7 nAChRs may undergo dynamic regulation, with insertion into the synapse and subsequent internalization. The widespread and substantial expression of alpha7 nAChRs at synapses in the hippocampus is consistent with an important role in mediating and/or modulating synaptic transmission, plasticity, and neurodegeneration.

Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus.

Age-dependent cognitive impairments have been correlated with functional and structural modifications in the hippocampal formation. In particular, the brain endogenous steroid pregnenolone-sulfate (Preg-S) is a cognitive enhancer whose hippocampal levels have been linked physiologically to cognitive performance in senescent animals. However, the mechanism of its actions remains unknown. Because neurogenesis is sensitive to hormonal influences, we examined the effect of Preg-S on neurogenesis, a novel form of plasticity, in young and old rats. We demonstrate that in vivo infusion of Preg-S stimulates neurogenesis and the expression of the polysialylated forms of NCAM, PSA-NCAM, in the dentate gyrus of 3- and 20-month-old rats. These influences on hippocampal plasticity are mediated by the modulation of the gamma-aminobutyric acid receptor complex A (GABA(A)) receptors present on hippocampal neuroblasts. In vitro, Preg-S stimulates the division of adult-derived spheres suggesting a direct influence on progenitors. These data provide evidence that neurosteroids represent one of the local secreted signals controlling hippocampal neurogenesis. Thus, therapies which stimulate neurosteroidogenesis could preserve hippocampal plasticity and prevent the appearance of age-related cognitive disturbances.

Chronic restraint stress down-regulates amygdaloid expression of polysialylated neural cell adhesion molecule.

The amygdala is a brain area which plays a decisive role in fear and anxiety. Since exposure to chronic stress can induce profound effects in emotion and cognition, plasticity in specific amygdaloid nuclei in response to prior stress has been hypothesized to account for stress-induced emotional alterations. In order to identify amygdala nuclei which may be affected under chronic stress conditions we evaluated the effects of 21-days chronic restraint stress on the expression of a molecule implicated crucially in alterations in structural plasticity: the polysialylated neural cell adhesion molecule. We found that polysialylated neural cell adhesion molecule-immunoreactivity within the amygdala, present in somata and neuronal processes, has a regional gradient with the central medial and medial amygdaloid nuclei showing the highest levels. Our results demonstrate that chronic restraint stress induced an overall reduction in polysialylated neural cell adhesion molecule-immunoreactivity in the amygdaloid complex, mainly due to a significant decrease in the central medial amygdaloid and medial amygdaloid nuclei. Our data suggest that polysialylated neural cell adhesion molecule in these nuclei may play a prominent role in functional and structural remodeling induced by stress, being a potential mechanism for cognitive and emotional modulation. Furthermore, these finding provide the first clear evidence that life experiences can regulate the expression of polysialylated neural cell adhesion molecule in the amygdaloid complex.

Stress suppresses and learning induces plasticity in CA3 of rat hippocampus: a three-dimensional ultrastructural study of thorny excrescences and their postsynaptic densities.

Chronic stress and spatial training have been proposed to affect hippocampal structure and function in opposite ways. Previous morphological studies that addressed structural changes after chronic restraint stress and spatial training were based on two-dimensional morphometry which does not allow a complete morphometric characterisation of synaptic features. Here, for the first time in such studies, we examined these issues by using three-dimensional (3-D) reconstructions of electron microscope images taken from thorny excrescences of hippocampal CA3 pyramidal cells. Ultrastructural alterations in postsynaptic densities (PSDs) of thorny excrescences receiving input from mossy fibre boutons were also determined, as were changes in numbers of multivesicular bodies (endosome-like structures) within thorny excrescences and dendrites. Quantitative 3-D data demonstrated retraction of thorny excrescences after chronic restraint stress which was reversed after water maze training, whilst water maze training alone increased thorny excrescence volume and number of thorns per thorny excrescence. PSD surface area was unaffected by restraint stress but water maze training increased both number and area of PSDs per thorny excrescence. In restrained rats that were water maze trained PSD volume and surface area increased significantly. The proportion of perforated PSDs almost doubled after water maze training and restraint stress. Numbers of endosome-like structures in thorny excrescences decreased after restraint stress and increased after water maze training. These findings demonstrate that circuits involving contacts between mossy fibre terminals and CA3 pyramidal cells at stratum lucidum level are affected conversely by water maze training and chronic stress, confirming the remarkable plasticity of CA3 dendrites. They provide a clear illustration of the structural modifications that occur after life experiences noted for their different impact on hippocampal function.

Three-dimensional reconstruction of synapses and dendritic spines in the rat and ground squirrel hippocampus: new structural-functional paradigms for synaptic function.

Published data are reviewed along with our own data on synaptic plasticity and rearrangements of synaptic organelles in the central nervous system. Contemporary laser scanning and confocal microscopy techniques are discussed, along with the use of serial ultrathin sections for in vivo and in vitro studies of dendritic spines, including those addressing relationships between morphological changes and the efficiency of synaptic transmission, especially in conditions of the long-term potentiation model. Different categories of dendritic spines and postsynaptic densities are analyzed, as are the roles of filopodia in originating spines. The role of serial ultrathin sections for unbiased quantitative stereological analysis and three-dimensional reconstruction is assessed. The authors' data on the formation of more than two synapses on single mushroom spines on neurons in hippocampal field CA1 are discussed. Analysis of these data provides evidence for new paradigms in both the organization and functioning of synapses.

Altered visual processing in a rodent model of Attention-Deficit Hyperactivity Disorder.

A central component of Attention-Deficit Hyperactivity Disorder (ADHD) is increased distractibility, which is linked to the superior colliculus (SC) in a range of species, including humans. Furthermore, there is now mounting evidence of altered collicular functioning in ADHD and it is proposed that a hyper-responsive SC could mediate the main symptoms of ADHD, including distractibility. In the present study we have provided a systematic characterization of the SC in the most commonly used and well-validated animal model of ADHD, the spontaneously hypertensive rat (SHR). We examined collicular-dependent orienting behavior, local field potential (LFP) and multiunit responses to visual stimuli in the anesthetized rat and morphological measures in the SHR in comparison to the Wistar Kyoto (WKY) and Wistar (WIS). We found that SHRs remain responsive to a repeated visual stimulus for more presentations than control strains and have a longer response duration. In addition, LFP and multiunit activity within the visually responsive superficial layers of the SC showed the SHR to have a hyper-responsive SC relative to control strains, which could not be explained by altered functioning of the retinocollicular pathway. Finally, examination of collicular volume, neuron and glia densities and glia:neuron ratio revealed that the SHR had a reduced ratio relative to the WKY which could explain the increased responsiveness. In conclusion, this study demonstrates strain-specific changes in the functioning and structure of the SC in the SHR, providing convergent evidence that the SC might be dysfunctional in ADHD.

Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome.

Hippocampal pathology is likely to contribute to cognitive disability in Down syndrome, yet the neural network basis of this pathology and its contributions to different facets of cognitive impairment remain unclear. Here we report dysfunctional connectivity between dentate gyrus and CA3 networks in the transchromosomic Tc1 mouse model of Down syndrome, demonstrating that ultrastructural abnormalities and impaired short-term plasticity at dentate gyrus-CA3 excitatory synapses culminate in impaired coding of new spatial information in CA3 and CA1 and disrupted behavior in vivo. These results highlight the vulnerability of dentate gyrus-CA3 networks to aberrant human chromosome 21 gene expression and delineate hippocampal circuit abnormalities likely to contribute to distinct cognitive phenotypes in Down syndrome.

Cerebral Glycoprotein Synthesis and Long-term Memory Formation in the Chick (Gallus domesticus) Following Passive Avoidance Training Depends on the Nature of the Aversive Stimulus.

Chicks that peck a small bright bead coated in a distateful substance can learn in a single trial to subsequently avoid a similar bead. The taste aversant commonly used is methyl anthranilate, which also has a strong pervasive odour. We have compared the efficacy of methyl anthranilate and the apparently odourless quinine as aversants. Methyl anthranilate-trained chicks learnt the task and the memory apparently persisted undiminished for at least 24 h. Quinine-trained chicks exhibited a memory for the task similar to that of methyl anthranilate-trained chicks 45 min after training, this thereafter declined until, at 24 h after training, they showed no recall. We investigated the incorporation of a radio-labelled synaptic membrane glycoprotein precursor, [3H]fucose, into three regions of the chick forebrain; two of these regions have previously been implicated in learning using methyl anthranilate as the aversant. There was a significant increase in [3H]fucose incorporation into the left lateral cerebral area and numerically similar, but non-significant, increases in the intermediate part of the medial hyperstriatum ventrale and lobus parolfactorius. There were no such increases in the right hemisphere of methyl anthranilate-trained chicks or any region of either hemisphere of quinine-trained chicks. Thus, the memory for methyl anthranilate is longer-lasting than that for quinine and is associated with increased fucosylation in the left cerebral hemisphere and although in the short-term, chicks can retain a memory of the one-trial passive avoidance task with quinine as the aversant, this does not result in a localized increase in cerebral [3H]fucose incorporation.

Distribution of mu, delta, and kappa opioid receptor binding sites in the brain of the one-day-old domestic chick (Gallus domesticus): an in vitro quantitative autoradiographic study.

Three highly specific opioid ligands--[D-Ala2,Gly-ol]-enkephalin (DAGO) for mu (mu) receptor sites, [D-Pen2,D-Pen5]-enkephalin (DPDPE) for delta (delta) sites, and U-69593 for kappa (kappa) sites--were used to determine the regional distribution of the three major subtypes of opioid receptor binding sites in the brains of 1-day-old domestic chicks by the technique of quantitative receptor autoradiography. Whilst there was a degree of heterogeneity in the binding levels of each of the ligands, some notable similarities existed in the binding of the mu and kappa ligands in several forebrain regions, and in the optic tectum of the midbrain where mu and delta binding was very high. In the forebrain there was a high level of binding of mu and kappa ligands in the hyperstriatum, and for the mu ligand there was a very distinct lamination of binding sites in hyperstriatum accessorium, intercalatum supremum, dorsale and ventrale. Levels of binding of the mu and kappa ligands were also high in nucleus basalis, and (for mu only) in the neostriatum. The distribution of binding of the delta specific ligand in the forebrain showed marked differences to that of mu and kappa, being particularly low in the hyperstriatum and neostriatum. Very high levels of labelling of delta binding sites were, however, found in the nucleus rotundus. Binding of the three ligands was generally low or absent in the cerebellum and medulla, apart from a distinct labelling of the granule cell layer by the mu-ligand. A kinetic analysis was made of the binding of the three ligands to whole forebrain sections using scintillation counting methods.(ABSTRACT TRUNCATED AT 250 WORDS)