Altered hippocampal circuit function in C3H alpha7 null mutant heterozygous mice.

The alpha7 subtype of nicotinic receptor is highly expressed in the hippocampus where it is purported to modulate release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The alpha7 receptor-mediated release of GABA is thought to contribute to hippocampal inhibition (gating) of response to repetitive auditory stimulation. This hypothesis is supported by observations of hippocampal auditory gating deficits in mouse strains with low levels of hippocampal alpha7 receptors compared to strains with high levels of hippocampal alpha7 receptors. The difficulty with comparisons between mouse strains, however, is that different strains have different genetic backgrounds. Thus, the observed interstrain differences in hippocampal auditory gating might result from factors other than interstrain variations in the density of hippocampal alpha7 receptors. To address this issue, hippocampal binding of the alpha7 receptor-selective antagonist alpha-bungarotoxin as well as hippocampal auditory gating characteristics were compared in C3H wild type and C3H alpha7 receptor null mutant heterozygous mice. The C3H alpha7 heterozygous mice exhibited significant reductions in hippocampal alpha7 receptor levels and abnormal hippocampal auditory gating compared to the C3H wild type mice. In addition, a general increase in CA3 pyramidal neuron responsivity was observed in the heterozygous mice compared to the wild type mice. These data suggest that decreasing hippocampal alpha7 receptor density results in a profound alteration in hippocampal circuit function.

Schizophrenia trials in China: a survey.

OBJECTIVE: China's biomedical research activity is increasing and this literature is becoming more accessible online. Our aim was to survey all randomized control schizophrenia trials (RCTs) in one Chinese bibliographic database. METHOD: Chinese Academic Journals was electronically searched for RCTs and all relevant citations were also sought on PubMed to ascertain global accessibility. RESULTS: The search identified 3275 records, of which 982 were RCTs relevant to schizophrenia. A total of 71% (699) could be found by using English phrases. All the main body of text of the 982 papers was in Mandarin. On average, these trials involved about 100 people, with interventions and outcome measures familiar to schizophrenia trialists worldwide. Four of the 982 records (<1%) were identified on PubMed. CONCLUSION: Those undertaking systematic reviews should search the Chinese literature for relevant material. Failing to do this will leave the results of systematic reviews prone to random error or bias, or both.

Inhibition of nitric oxide synthase prevents alpha 7 nicotinic receptor-mediated restoration of inhibitory auditory gating in rat hippocampus.

The hippocampus rapidly inhibits its response to repetitive auditory stimulation, an example of an auditory sensory gating mechanism involved in human psychopathology. The neuronal basis of this inhibitory gating mechanism has been investigated in rats. Activation of the alpha 7 nicotinic receptor is required. alpha 7 nicotinic receptor activation also releases nitric oxide in the hippocampus and blockade of nitric oxide synthase reduces inhibitory gating of auditory response. There has not been a direct demonstration that blockade of nitric oxide synthase specifically prevents alpha 7 nicotinic receptor activation of the inhibition of auditory response. Therefore, the goal of the present study was to determine whether this functional effect of alpha 7 receptor activation requires release of nitric oxide. Lesions of the fimbria-fornix disrupt auditory gating by preventing cholinergic stimulation of the hippocampus. Following recovery from this surgery, rats were administered 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A; 10 mg/kg, sc), an agonist at the alpha 7 receptor. DMXB-A restored auditory gating in the fimbria-fornix-lesioned rats, indicating that activation of the alpha 7 nicotinic receptor alone is sufficient to restore auditory gating following lesions of the fimbria-fornix. However, intracerebroventricular infusion of N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, blocked the DMXB-A-mediated restoration of auditory gating; infusion of the inactive D-enantiomer did not. Restoration of auditory gating by DMXB-A in the fimbria-fornix-lesioned rats was blocked by intracerebroventricular infusion of alpha-bungarotoxin, but not by mecamylamine or dihydro-beta-erythroidine. Together, these data support the hypothesis that nitric oxide mediates alpha 7 nicotinic receptor activation of gating of auditory response in rat hippocampus.

Kainic acid lesions in adult rats as a model of schizophrenia: changes in auditory information processing.

Previous studies have suggested that intracerebroventricular kainic acid injections alter brain anatomy and neurochemistry in a manner similar to what is observed in schizophrenic patients. Disturbances in sensory information processing are one of the major symptoms of schizophrenia. Thus, the present experiments were designed to evaluate the hypothesis that hippocampal damage, induced by administration of kainic acid, would alter the processing of auditory stimuli in a paired-click paradigm. Adult male Sprague-Dawley rats were implanted for surface recording of auditory evoked potentials. At the time of electrode implantation, the rats also received bilateral injections of either kainic acid or the vehicle solution. In vehicle-treated rats, the midlatency N40 component of the auditory evoked potential was diminished in amplitude by approximately 60% in response to the second of a pair of clicks delivered 0.5 s apart. By contrast, no reduction of the N40 wave evoked by the second click was observed in kainate-treated rats. Further, administration of haloperidol, a prototypical neuroleptic agent, did not improve this auditory processing dysfunction in kainate-treated animals. Loss of auditory filtering in the paired-click paradigm and a lack of response to haloperidol in this test are typically observed in schizophrenic humans. Thus, the present results demonstrate that kainate-lesioned rats possess a functional schizophrenia-like abnormality, further reinforcing the utility of this model system for studying the basic neurobiology of schizophrenia-induced sensory processing deficits.

Randomized controlled trials in the Journal of Psychosomatic Research; 1956-1993: a prevalence study.

RCTs are the gold standard for the evaluation of mental health care [WHO Scientific Group on Treatment of Psychiatric Disorders, 1991]. All RCTs in the Journal of Psychosomatic Research to date (October 1993) were identified. A profile of the geographical origin, content, interventions under investigation, and methodological quality (as measured by reporting of randomization) of every trial is described. The prevalence of trials from Europe in the Journal is increasing. The frequency of trials regarding the psychotherapies in this journal is also increasing whilst that of drug trials is constant. High quality reporting of randomization is rare. This pilot study generates many disturbing questions regarding the content and quality of RCTs within psychosomatic medicine that urgently need to be answered. Trials in this journal may well not be representative of all RCTs relevant to psychosomatic medicine. If all such trials are to be made accessible to those interested in evidence-based practice, however, much methodical searching must be undertaken, and this study can then be repeated and the questions answered with more authority.

Sources of neostriatal cholecystokinin in the cat.

The objective of this study was to determine the sources of cholecystokinin within the neostriatum of the cat. Cholecystokinin-immunoreactive cells and fibers were detected by means of the peroxidase antiperoxidase immunohistochemical technique. This method was combined with intrastriatal injections of the retrograde marker horseradish peroxidase conjugated with wheat-germ agglutinin to survey the possible afferent sources of cholecystokinin to the feline neostriatum. Intrinsic, apparently aspiny cholecystokinin-immunoreactive neurons organized in a pericapsular pattern were found within both the caudate and putamen of the cat. In addition, both thalamostriatal and mesostriatal projections containing cholecystokinin were observed. These results indicate that cholecystokinin within the neostriatum of the cat arises from both intrinsic and extrinsic sites.

The effects of religious beliefs on the health care practices of the Amish.

The religious and cultural beliefs of the Amish result in many health care beliefs and practices which are significantly different from the dominant American culture. For example, the Amish are excluded from social security and health insurance coverage; they have different perceptions of health and illness; they do not practice birth control; they often lack the preventive practices of immunizations and prenatal care; and they may use a variety of traditional and nontraditional health care providers. Only by understanding the religiocultural belief system of this minority religious sect can nurse practitioners effectively meet the health care needs of their Amish patients.

PIP: An understanding of the religiocultural belief system of the Amish religious sect is essential if nurse practitioners are to meet the health care needs of Amish patients. The Amish are exempted from social security and reject health insurance coverage, do not practice birth control, and often veto preventive practices such as immunization and prenatal care. A nonjudgmental, open attitude is required on the part of health professionals to encourage Amish families to attend clinics where health monitoring can be maintained and health education provided. As a result of a view of illness that defines it in terms of a failure to function in the work role rather than as a set of symptoms, there is often a delay in seeking medical treatment. Amish men outlive Amish women, in part because of the high birth rate (average of 7 live births/woman). Birth control and abortion are forbidden by religious doctrine, even when pregnancy is life threatening. The Amish church has no rule against immunization, but only 16-26% of Amish children have received immunizations against the common childhood diseases. Reinforcing the rejection of preventive medicine is the low educational status of the Amish people; higher education is prohibited. This further implies that health instructions must be given in simple, clear language. Nurse practitioners must accept the fact that no amount of education will persuade Amish women to practice contraception. To continue to advocate family planning in the Amish community is to risk alienating couples from the health care system.