Biomedical subjects

J C Day

Publications and source records attributed to J C Day.

At least 19 recordsLinked to original sources

PubMed2001

Application of in vivo microdialysis to the study of cholinergic systems.

The application of in vivo microdialysis to the study of acetylcholine (ACh) release has contributed greatly to our understanding of cholinergic brain systems. This article reviews standard experimental procedures for dialysis probe selection and implantation, perfusion parameters, neurochemical detection, and data analysis as they relate to microdialysis assessments of cholinergic function. Particular attention is focused on the unique methodological considerations that arise when in vivo microdialysis is dedicated expressly to the recovery and measurement of ACh as opposed to other neurotransmitters. Limitations of the microdialysis technique are discussed, as well as methodological adaptations that may prove useful in overcoming these limitations. This is followed by an overview of recent studies in which the application of in vivo microdialysis has been used to characterize the basic pharmacology and physiology of cholinergic neurons. Finally, the usefulness of the microdialysis approach for testing hypotheses regarding the cholinergic systems' involvement in cognitive processes is examined. It can be concluded that, in addition to being a versatile and practical method for studying the neurochemistry of cholinergic brain systems, in vivo microdialysis represents a valuable tool in our efforts to better comprehend ACh's underlying role in a variety of behavioral processes.

Acetylcholine↗

PubMed2001

Neurotrophins differentially enhance acetylcholine release, acetylcholine content and choline acetyltransferase activity in basal forebrain neurons.

Several lines of evidence indicate that nerve growth factor is important for the development and maintenance of the basal forebrain cholinergic phenotype. In the present study, using rat primary embryonic basal forebrain cultures, we demonstrate the differential regulation of functional cholinergic markers by nerve growth factor treatment (24--96 h). Following a 96-h treatment, nerve growth factor (1--100 ng/mL) increased choline acetyltransferase activity (168--339% of control), acetylcholine content (141--185%), as well as constitutive (148--283%) and K(+)-stimulated (162--399%) acetylcholine release, but increased release was not accompanied by increased high-affinity choline uptake. Enhancement of ACh release was attenuated by vesamicol (1 microM), suggesting a vesicular source, and was abolished under choline-free conditions, emphasizing the importance of extracellular choline as the primary source for acetylcholine synthesized for release. A greater proportion of acetylcholine released from nerve growth factor-treated cultures than from nerve growth factor-naïve cultures was blocked by voltage-gated Ca(2+) channel antagonists, suggesting that nerve growth factor modified this parameter of neurotransmitter release. Cotreatment of NGF (20 ng/mL) with K252a (200 nM) abolished increases in ChAT activity and prevented enhancement of K(+)-stimulated ACh release beyond the level associated with K252a, suggesting the involvement of TrkA receptor signaling. Also, neurotrophin-3, neurotrophin-4 and brain-derived neurotrophic factor (all at 5--200 ng/mL) increased acetylcholine release, although they were not as potent as nerve growth factor and higher concentrations were required. High brain-derived neurotrophic factor concentrations (100 and 200 ng/mL) did, however, increase release to a level similar to nerve growth factor. In summary, long-term exposure (days) of basal forebrain cholinergic neurons to nerve growth factor, and in a less-potent fashion the other neurotrophins, enhanced the release of acetylcholine, which was dependent upon a vesicular pool and the availability of extracellular choline.

Acetylcholine↗

PubMed2000

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.

Animals↗

PubMed2000

Pharmacological characterization of endogenous acetylcholine release from primary septal cultures.

A detailed investigation of endogenous acetylcholine (ACh) release from primary embryonic septal cultures is described in this study. Applications of veratridine (25 microM) or increasing extracellular concentrations of K(+) (6-100 mM) induced robust increases of endogenous ACh release ( approximately 500-15,000 fmol/well/10 min). Release stimulated with K(+) (25 mM) was sustainable and did not differ significantly over 180 min. ACh release was dependent on extracellular choline and decreased proportionally to choline concentrations (0-10 microM). For example, after 30 min of stimulation with K(+) (25 mM), release in the absence of extracellular choline was approximately 25% of that associated with 10 microM choline. The vesicular transport blocker vesamicol (0-5 microM) almost completely prevented stimulated and basal ACh release at the highest concentration evaluated, which suggests a mostly vesicular mode of release in this model. The M(2)-like muscarinic receptor antagonist AF-DX 384 (0-10 microM) enhanced stimulated ACh release ( approximately 150% at the highest concentration evaluated), whereas the nonspecific muscarinic receptor agonist oxotremorine (0-10 microM) decreased stimulated release (approximately 60% at the highest concentration evaluated), suggesting that functional muscarinic autoreceptors exist in primary embryonic septal cultures. Novel findings concerning ACh release from primary embryonic septal cultures are reported herein, and the demonstration of ACh release gives further credit to the use of these cultures for studying cholinergic system functioning and in relation to physiology and pathology.

Acetylcholine↗

PubMed1999

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.

Acetylcholine↗

PubMed1999

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.

Animals↗

PubMed1998

Prenatal stress enhances stress- and corticotropin-releasing factor-induced stimulation of hippocampal acetylcholine release in adult rats.

There is growing evidence that stressors occurring during pregnancy can impair biological and behavioral responses to stress in the adult offspring. For instance, prenatal stress enhances emotional reactivity, anxiety, and depressive-like behaviors associated with a prolonged stress-induced corticosterone secretion and a reduction in hippocampal corticosteroid receptors. Among the neurotransmitters involved in these hormonal and behavioral responses, acetylcholine may play a critical role. However, it is unknown whether prenatal stressful events also may influence the development of cholinergic systems. In the present study, hippocampal acetylcholine was measured, by in vivo microdialysis, in both male and female adult prenatally stressed rats, under basal conditions, after a mild stress (saline injection) or after intracerebroventricular administration of corticotropin-releasing factor (CRF; 0.1 nM). No difference in basal release of acetylcholine was observed between control and prenatally stressed rats of both genders. Mild stress was found to increase hippocampal acetylcholine release to a greater extent in prenatally stressed rats than in controls. In males, the CRF-induced increase in hippocampal acetylcholine release was larger in prenatally stressed rats, as compared with controls, during the first hour after the injection and in females during the third hour after the injection. These data indicate that prenatal stress has long-term effects on the development of forebrain cholinergic systems. The augmented increase in hippocampal acetylcholine release after the mild stress and CRF injection in prenatally stressed rats may be involved in some of the hormonal and behavioral abnormalities found in prenatally stressed rats.

Acetylcholine↗

PubMed1998

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.

Adaptation, Psychological↗

PubMed1998

Corticotropin-releasing factor administered centrally, but not peripherally, stimulates hippocampal acetylcholine release.

In addition to corticotropin-releasing factor's well-known role in mediating hormonal and behavioral responses to stress, this peptide also reportedly affects arousal and cognition, processes that classically have been associated with forebrain cholinergic systems. Corticotropin-releasing factor stimulation of cholinergic neurons might thus provide a mechanism for this peptide's cognitive effects. To examine this possibility, the present experiments characterize the effect of corticotropin-releasing factor on cholinergic neurotransmission, using in vivo microdialysis to measure hippocampal acetylcholine release. Corticotropin-releasing factor (0.5-5.0 microg/rat intracerebroventricularly) was found to increase dialysate concentrations of acetylcholine in a dose-dependent manner in comparison with a control injection, the ovine peptide having a greater effect than the same dose of the human/rat peptide. This effect was found to be centrally mediated, independent of the peripheral effects of an exogenous corticotropin-releasing factor injection; subcutaneous injections of the peptide increased plasma concentrations of corticosterone, the adrenal hormone ultimately secreted in the rat's stress response, to the same level as did the central injections, without affecting hippocampal acetylcholine release. These results demonstrate that corticotropin-releasing factor, acting centrally, regulates hippocampal cholinergic activity, and suggest that corticotropin-releasing factor/acetylcholine interactions may underlie some of the previously identified roles of these neurotransmitters in arousal, cognition, and stress.

Acetylcholine↗

PubMed1998

A comparison of patients' and prescribers' beliefs about neuroleptic side-effects: prevalence, distress and causation.

Neuroleptic side-effects adversely affect clinical outcome in schizophrenic patients. Clinicians therefore require an understanding of the impact of such side-effects. This study compared psychiatrists' estimates of the prevalence of neuroleptic side-effects and associated distress with schizophrenic patients' reports of side-effects and distress. Psychiatrists were asked to estimate the likelihood of informing patients about side-effects. Psychiatrists' estimates of prevalence but not of distress correlated significantly with patients' reports. Psychiatrists' avowed decisions to inform patients about side-effects were significantly correlated with their estimates of prevalence and distress, but not with patients' reported levels of distress. Patients were unlikely to attribute side-effects to neuroleptic medication. These results indicate that patients and psychiatrists share similar views about the prevalence and implications of neuroleptic side-effects. However, psychiatrists' apparent lack of understanding of which side-effects are most likely to cause distress to patients may adversely affect the therapeutic alliance between prescribers and consumers.

Adult↗

PubMed1997

Cocaine-induced increase in cortical acetylcholine release: interaction with the hypothalamo-pituitary-adrenal axis.

An influence on drug-taking behaviours of the stress-related hypothalamo-pituitary-adrenal (HPA) axis and its final hormonal mediator, corticosterone, has previously been demonstrated. A role for cortically projecting cholinergic neurons in these behaviours can also be proposed. The experiments presented here examine the effect of the drug of abuse cocaine (15 mg/kg) on the release of acetylcholine (ACh) in the cortex of freely moving rats, using the technique of in vivo microdialysis. To assess a possible modulatory influence of the HPA axis via its final hormonal mediator corticosterone, the cocaine-induced effect on cortical ACh release in intact rats was compared to that in adrenalectomized (ADX) rats, which thus lacked their endogenous source of corticosterone, and in ADX rats in which the cocaine-induced corticosterone peak and/or the basal circadian concentrations of serum corticosterone were simulated by replacement treatments. The results reported here demonstrate that cortical ACh release is greatly increased by cocaine in intact rats; ADX prolongs the return to basal levels of cortical ACh, and the chronic replacement of circadian levels of corticosterone normalizes this effect. In contrast, during the plateau period of cocaine-induced increased cortical ACh release, where no effect of ADX is evident, rats with chronic replacement of corticosterone show an attenuated cocaine-induced cortical ACh release, and the acute replacement of the cocaine-induced corticosterone secretion further attenuates this response. These results demonstrate that cocaine stimulates cortically projecting cholinergic neurons, and that the HPA hormone corticosterone modulates this interaction in a complex manner which merits further investigation.

Acetylcholine↗

PubMed1996

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.

Adult↗

PubMed1995

A self-rating scale for measuring neuroleptic side-effects. Validation in a group of schizophrenic patients.

BACKGROUND: A study was conducted to validate a comprehensive self-rating scale for measuring side-effects of neuroleptic drugs. METHOD: The Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), which includes 'red herring' items, was twice administered to 50 DSM-III-R schizophrenic patients, who were also interviewed using the UKU side-effect rating scale; 50 unmedicated controls also completed the LUNSERS: RESULTS: The test-retest reliability of the LUNSERS was good (r = 0.811, P < 0.001) as was its concurrent validity against the UKU (r = 0.828, P < 0.001). Scores correlated with chlorpromazine equivalent doses (r = 0.310, P < 0.02). ROC analysis demonstrated that the scale discriminated between patients and non-medicated controls, who scored differently for real side-effects but not for 'red herring' items. CONCLUSIONS: The LUNSERS is an efficient, reliable and valid method of assessing neuroleptic side-effects.

Adult↗

PubMed1994

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.

Acetylcholine↗

PubMed1994

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.

Acetylcholine↗

PubMed1994

Toward a physical map of human chromosome 10: isolation of 183 YACs representing 80 loci and regional assignment of 94 YACs by fluorescence in situ hybridization.

One hundred eighty-three YACs carrying human chromosome 10 sequences were isolated from multigenome equivalent libraries by PCR-based screening for the presence of 80 different chromosome 10-specific STSs. Ninety-four of the isolated YACs, representing 52 genes and DNA segments, were mapped to regions of chromosome 10 by fluorescence in situ hybridization. The results localized 26 DNA segments to cytogenetic bands for the first time. About 37% (35/94) of the YACs hybridized to more than one chromosomal location: 31 to other chromosomes in addition to chromosome 10 and 4 to 2 distinct locations on chromosome 10. These results are consistent with the number of chimeric YACs expected from these libraries but may also reflect the presence of 2 or more YACs within a single clone or the presence of low copy repeated elements within the genome. This STS anchor screening effort resulted in the identification of 69 contigs, with 7 contigs consisting of 2 anchors each and 1 contig consisting of 5 anchors. All linked STSs were multiply linked by at least 2 independent YACs. These anchored YACs span the entire chromosome and appear to cover 15% of chromosome 10.

Chromosome Mapping↗

PubMed1994

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.

Acetylcholine↗

PubMed1994

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.

Acetylcholine↗