Maternal care, hippocampal synaptogenesis and cognitive development in rats.

We report that variations in maternal care in the rat promote hippocampal synaptogenesis and spatial learning and memory through systems known to mediate experience-dependent neural development. Thus, the offspring of mothers that show high levels of pup licking and grooming and arched-back nursing showed increased expression of NMDA receptor subunit and brain-derived neurotrophic factor (BDNF) mRNA, increased cholinergic innervation of the hippocampus and enhanced spatial learning and memory. A cross-fostering study provided evidence for a direct relationship between maternal behavior and hippocampal development, although not all neonates were equally sensitive to variations in maternal care.

Mental health practitioner's attitude towards maintenance neuroleptic treatment for people with schizophrenia.

Pharmacological relapse prevention treatment for people with schizophrenia can last for years if not the person's lifetime. The attitude mental health practitioners (MHPs) hold regarding this treatment can have profound effects on service users' decisions related to treatment. The small number of studies focusing on this issue concentrates on the use of 'depot' preparations. To develop a validated inventory to assess the attitudes of MHPs towards treatment and evaluate the attitudes of a sample of MHPs. The inventory was developed in three stages; item selection, piloting and psychometric testing. The validated inventory was administered to a sample of 50 MHPs undertaking a degree level course in the psycho-social management of psychosis. The final inventory consisted of 21 attitudinal items and four items related to the practitioner's confidence. Results from the sample revealed areas of agreement, variation and uncertainty. A valid and reliable inventory has been developed. The administration of the inventory to 50 MHPs returned results which reflect variable attitudes and perceptions of competency towards maintenance neuroleptic treatment. This diversity in attitudes may have an impact on management of people with a diagnosis of schizophrenia and clinical outcomes.

Enhanced acetylcholine release in hippocampus and cortex during the anticipation and consumption of a palatable meal.

In rats trained for 14 days to consume a palatable liquid chocolate meal (Sustacal), in vivo brain microdialysis was used to measure release of acetylcholine in the frontal cortex and hippocampus during anticipation and consumption of the meal. Rats were trained in an experimental chamber in which they were separated from the Sustacal by a screen for 20 min (trained, rewarded group). The screen was then removed and the rats were allowed 20 min of access to the meal. Two control groups were run concurrently: these groups consisted of rats (i) that were trained over 14 days but only had access to water in the experimental chamber (trained, non-rewarded), or (ii) that were introduced into the experimental chamber for the first time on the final test (i.e. dialysis) session, and presented with Sustacal (naive). Different results were obtained in the hippocampus and frontal cortex. In the hippocampus there were no group differences with respect to acetylcholine release. Thus, in all three groups acetylcholine release increased to about 220% of basal values when animals were placed in the experimental chamber. In the frontal cortex, acetylcholine release also increased significantly in all three groups. However, the extent of this increase was significantly greater in the trained, rewarded group, reaching approximately 300% of basal values during the anticipatory and consummatory components of the task. The significant increases in acetylcholine release which occurred in both the hippocampus and frontal cortex of each of the three groups are consistent with an involvement of cholinergic basal forebrain neurons in the regulation of arousal or attention. In addition, however, acetylcholine release in the frontal cortex can be further selectively enhanced by the animal's past training experience, perhaps being associated with the anticipation of reward.

The potent and selective dopamine D1 receptor agonist A-77636 increases cortical and hippocampal acetylcholine release in the rat.

The effects of systemic administration of the full dopamine D1 receptor agonist A-77636 on acetylcholine release in rat frontal cortex and hippocampus were studied using in vivo microdialysis. Administration of A-77636 (4 mumol/kg s.c.) greatly (> 230%) increased both cortical and hippocampal acetylcholine release for more than 3 h; at a lower dose (1 mumol/kg s.c.) A-77636 significantly stimulated cortical but not hippocampal acetylcholine release. The effect of the higher dose of A-77636 on cortical acetylcholine release was blocked by the dopamine D1 receptor antagonist SCH 23390 (300 micrograms/kg s.c.). These results confirm that stimulation of dopamine D1 receptors facilitates cortical and hippocampal acetylcholine release in vivo, and indicate that these two structures are differentially sensitive to this effect. They also raise the possibility that dopamine D1 receptor agonists may be useful in the treatment of cortical and hippocampal acetylcholine deficit-related syndromes.

A novel muscarinic M(4) receptor antagonist provides further evidence of an autoreceptor role for the muscarinic M(2) receptor sub-type.

Muscarinic M(2) (AF-DX 384, BIBN-161) and M(4) (PD102807) receptor antagonists were used to investigate the respective roles of these two receptor sub-types in the regulation of acetylcholine release in the rat hippocampus. In vivo dialysis studies revealed that only the muscarinic M(2) receptor antagonists significantly and concentration-dependently facilitate acetylcholine release. The newly developed muscarinic M(4) receptor antagonist was unable to regulate acetylcholine release except at the highest concentration tested. It would thus appear that the muscarinic receptor acting as negative autoreceptor in the rat hippocampus is of the muscarinic M(2) sub-type, the role of the muscarinic M(4) receptor being minimal in this regard.

Dopamine depletion attenuates amphetamine-induced increases of cortical acetylcholine release.

The extent to which the d-amphetamine (2.0 mg/kg)-induced increase in cortical acetylcholine release is mediated by dopamine and/or noradrenaline was assessed using in vivo microdialysis in freely moving rats. Unilateral 6-hydroxydopamine lesions of the mesotelencephalic dopaminergic system, which depleted forebrain dopamine by 99% on the lesioned side, significantly attenuated the effect of d-amphetamine on cortical acetylcholine release compared to a surgical control group (160% baseline vs. 270%), suggesting that dopamine at least in part mediates this effect of d-amphetamine. In contrast, bilateral 6-hydroxydopamine lesions of the dorsal noradrenergic bundle which depleted forebrain noradrenaline by at least 95% had no effect on d-amphetamine-stimulated cortical acetylcholine release. These results point to an important role for forebrain dopamine in the regulation of cortically projecting cholinergic neurons and fail to support the hypothesis that the ascending noradrenergic projections of the locus coeruleus are significantly involved.

The meaning and management of neuroleptic medication: a study of patients with a diagnosis of schizophrenia.

The meaning of medication and the way in which people use medicines has been the focus of a number of studies in recent years. However, there has been little attention directed to the meaning and management of neuroleptic medication by people who have received a diagnosis of schizophrenia. This topic is highly relevant to policy because of the central role given to neuroleptics in contemporary mental health and community care services. Using data from in-depth interviews with people with a diagnosis of schizophrenia we explore patients reasons for taking neuroleptics and the ways in which patients self-regulate their medication. The data suggest that the main utility of taking neuroleptic medication is to control specific symptoms and to gain personal control over managing symptoms. The costs of taking medication were side-effects which at times equalised or outweighed the positive gains of the neuroleptic medication. Patient accounts suggest that everyday medication practices are to a significant degree related to a policy context which stresses the need to survey and control the behaviour of people living in the community and the wider meaning and symbolic significance that schizophrenia has for patients in their everyday lives. For this reason, self regulatory action in this group of patients tends to be less evident and the threat of external social control greater than patients taking medication for other chronic conditions. The findings suggest the need to develop a collaborative patient-centred model of medication management for patients diagnosed with schizophrenia.

Behavioral pharmacology and biochemistry of central cholinergic neurotransmission.

Systemically administered cholinergic (muscarinic) receptor antagonists can impair the acquisition and post-acquisition performance of a variety of learned behaviors. acquisition performance of a variety of learned behaviors. At present, there is no consensus about the psychological mechanisms underlying these deficits. Behavioral inhibition, working (short-term) memory, reference (long-term) memory, attention, movement and strategy selection, and stimulus processing are among the constructs that have been proposed as underlying the effects of muscarinic receptor blockade. On the basis of neuroanatomical and neuropharmacological considerations it is contended that debates about the nature of the mediating events are pointless because they are on an anatomy that does not exist. Specifically, given that cholinergic neurons innervate almost the entire neuraxis and that muscarinic cholinergic receptors are distributed throughout the central nervous system, it is virtually certain that systemically applied antimuscarinic drugs will influence a broad spectrum of brain functions. In addition, the nature of the deficits produced by scopolamine and atropine, which are competitive antagonists, will depend on the regional endogenous rate of acetylcholine release, which may in turn be influenced by the particular environment and/or level of training imposed on the animal. As the literature seems to indicate, therefore, the effects of competitive antagonists will vary as a function of both the behavioral test and the level of training. Accordingly, attempts at unitary formulations of central cholinergic function are ill-conceived and illusory. Another approach to understanding central cholinergic function has been based on the use of local injections of excitotoxins into brain regions such as the basal forebrain that contain cholinergic neurons. Recent published reports indicate, that many of the behavioral deficits observed after ibotenic acid lesions of the basal forebrain are due primarily to the loss of non-cholinergic neurons. The inherent limitations of the excitotoxin lesion approach for unravelling the functions of central cholinergic systems are such that they cannot produce definitive information and might best, therefore, be abandoned. At present, a reliable selective toxin for cholinergic neurons is not available and urgently required. Until such a compound is identified, local intracerebral applications of antimuscarinic agents may be the preferred procedure for studying the behavioral correlates of regional blockade of cholinergic activity. Brain microdialysis in freely moving animals also holds considerable promise with respect to defining the circumstances under which acetylcholine is released in discrete regions of the central nervous system. At present, the function of central cholinergic systems and the possible role of each in learning and memory remain poorly understood.

Consent and long-term neuroleptic treatment.

The involvement of clients in the process of developing their care and treatment package is well established. If a genuine collaboration in treatment is achieved one of the fundamental bases of this process lies with 'informed consent'. Neuroleptic medication forms the basis of relapse prevention treatment for people suffering from schizophrenia with non-adherence to treatment seen as the largest cause of relapse. This paper reviews the complex and difficult issues in obtaining informed consent for this client group from within the context of the nurse's role and the problems that arise as a consequence of the blurring of professional boundaries. Throughout the paper reference is made to the expectations made by the UKCC, which provides clarification of nurses' practice in this area.

A miniature confocal Raman probe for endoscopic use.

Raman spectroscopy is a powerful tool for studying biochemical changes in the human body. We describe a miniature, confocal fibre optic probe intended to fit within the instrument channel of a standard medical endoscope. This probe has been optimized for the study of the carcinogenesis process of oesophageal malignancy. The optical design and fabrication of this probe is described including the anisotropic wet etching technique used to make silicon motherboards and jigs. Example spectra of PTFE reference samples are shown. Spectra with acquisition times as low as 2 s from resected oesophageal tissue are presented showing identifiable biochemical changes from various pathologies.

Implementation of resource management plans: identifying keys to success.

One of the primary challenges in resource and environmental planning is successful implementation of plans. Plan implementation is a complex process influenced by many factors. This study identifies 19 criteria affecting implementation success and tests the impact of these criteria through a case study of collaborative plan implementation in British Columbia, Canada. The significance of criteria and degree to which they are met is assessed by a survey of senior officials responsible for plan implementation. An implementation evaluation index (IEI) is constructed to assess the quality of plan implementation systems and best practices for effective implementation are identified.

Confirmation of the species status of the blackfly Simulium galeratum in Britain using molecular taxonomy.

Since 1920 Simulium reptans (Linnaeus) (Diptera: Simuliidae) has been reported as exhibiting two different larval morphotypes, a typical S. reptans and an atypical S. reptans var. galeratum, which differ in the markings of the larval head capsule. Inconsistent variation in adults and no apparent variation in the pupae have led taxonomists to conclude that these types in Britain are a single species. We investigated populations in Britain where either the typical form or var. galeratum is found, and one population where the two exist sympatrically. A phylogenetic study based upon a region of the mitochondrial cytochrome c oxidase 1 gene (DNA barcoding) produced a tree that delineated the morphotypes into two distinct monophyletic clades. The average Kimura-2-parameter distances within each clade (i.e. within each morphotype) were very low (0.67% and 0.78%), with the distances between morphotypes being 9-10-fold greater (mean 7.06%). This is concordant with differences within and between species in other taxa; based upon the strict correlation between the molecular variation and the morphotypes, we propose the re-instatement of S. galeratum to species status.

Structure and evolution of the luciferin-regenerating enzyme (LRE) gene from the firefly Photinus pyralis.

To study the structural features of genes for the luciferin-regenerating enzyme (LRE), the entire gene along with 524 bp of upstream sequence was determined from Photinus pyralis (Coleoptera: Lampyridae). The LRE gene revealed an open reading frame composed of five exons divided by four introns ranging in size from 47 to 904 bp. The deduced LRE amino acid sequence showed identity to senescence marker protein-30 (SMP30) from a number of insects and mammals including four putative SMP30 sequences from Anopheles gambiae. Gene structure comparisons showed some intron/exon site conservation with A. gambiae and mammalian SMP30 proteins but not Drosophila. LRE and luciferase sequence comparisons revealed two conserved putative luciferin-binding sites. The evolution of LRE was discussed in relation to its function.

Dopaminergic regulation of septohippocampal cholinergic neurons.

The extent to which acetylcholine (ACh) release in the hippocampus is regulated by dopaminergic mechanisms was assessed using in vivo microdialysis in freely moving rats. Systemic administration of the dopamine (DA) receptor agonist apomorphine (1.0 mg/kg) or the specific D1 agonist CY 208-243 (1.0 mg/kg) increased microdialysate concentrations of ACh in the hippocampus. The D2 receptor agonist quinpirole (0.5 mg/kg) produced a small but statistically significant decrease in hippocampal ACh release. d-Amphetamine (2.0 mg/kg) increased ACh release, an effect that was blocked by the D1 receptor antagonist SCH 23390 (0.3 mg/kg) but not by the D2 antagonist raclopride (1.0 mg/kg). These findings suggest that endogenous DA stimulates septohippocampal cholinergic neurons primarily via actions at D1 receptors. In addition, these results are similar to previous findings regarding the dopaminergic regulation of cortical ACh release, and suggest that the anatomical continuum formed by basal forebrain cholinergic neurons that project to the cortex and hippocampus acts as a functional unit, at least with respect to its regulation by DA.

Relative abundance, isolation and structure of phlebotomine microsatellites.

Popular classes of microsatellites are not always abundant in insects or easily isolated from them. Dotblot hybridizations demonstrated much variation in the relative abundance of four repeat classes in four phlebotomine sandfly species. Only AAT-class repeats were specifically isolated from a phagemid library of Lutzomyia whitmani, even though other microsatellites had similar abundances. An enrichment step would have targeted classes but was omitted because relatively long flanking sequences were sought. All fourteen sandfly loci had a non-coding structure, and a minority of dipteran AAT-class repeats found in DNA databases and the literature were from exons. Therefore, this class should often provide neutral alleles for population studies. Perfect, not imperfect, AAT-class repeats were polymorphic in wild L. whitmani.

Schizophrenic patients' experiences of neuroleptic medication: a Q-methodological investigation.

Q-methodology was used to explore the experiences of 50 medicated schizophrenic patients. Four main factors were identified. Participants loading on the first factor agreed with statements suggesting an uncomplaining attitude towards their medication and also with statements indicating a dependent attitude towards the medical profession. Those loading on the second factor endorsed statements indicative of a sceptical attitude towards medication, together with a concern for personal autonomy. Participants loading on the third factor had apparently made a balanced appraisal of the advantages and disadvantages of their medication, whereas those who loaded positively on the final factor reported positive benefits of medication but a sceptical attitude towards medical advice. The study highlights the complexity of psychiatric patients' attitudes to treatment.