Guiding the way to public health improvement: exploring the connections between The Community Guide's Evidence-Based Interventions and health department accreditation standards.

CONTEXT: Recent years have seen rising interest in initiatives that focus on public health improvement. This includes support for accreditation of public health departments-administered by the Public Health Accreditation Board (PHAB)-and increasing expectations that health departments should use evidence-based programs, services, and policies (interventions) such as those described in The Guide to Community Preventive Services (The Community Guide). OBJECTIVE: This project was initiated to explore the potential connections between Community Guide interventions and PHAB domains, standards, and measures. DESIGN: The project team focused on developing a Crosswalk tool to assist health departments in identifying evidence-based interventions from The Community Guide whose implementation could help document conformity with PHAB domains, standards, and measures. All Community Preventive Services Task Force-recommended interventions were reviewed to determine whether they reflect the intent and requirements of the PHAB standards and measures. MAIN OUTCOME MEASURES: Three types of connections were defined through which Community Guide interventions could be relevant to the required documentation for a PHAB measure. All instances of these connections were identified and included in the Crosswalk. RESULTS: The Crosswalk tool consists of 2 tables. The first table cross-references individual PHAB domains, standards, and measures with interventions from The Community Guide that could help provide documentation for accreditation. The second table can help accreditation preparation staff to engage with program staff. It is searchable by Community Guide topic, identifying the PHAB measures that relate to each Community Guide intervention within that topic. The type, location, and extent of connections between Community Guide interventions and PHAB domains, standards, and measures are presented and discussed. CONCLUSIONS: Tools such as the Crosswalk can be instrumental in advancing the use of evidence-based interventions in public health practice.

Sex-Related Effect of Aging in Gingival Gamma-Delta T Cells.

Aging affects the number and function of gamma-delta (γδ) T cells in a tissue-specific manner, modifying the risk for inflammatory disease. These aging-related γδT-cell variations in gingival tissues that could increase the risk for inflammation and periodontal disease remain unknown. Here we sought to identify quantitative and qualitative variations in gingival γδT cells associated with aging that could have an impact in oral immunoinflammatory responses. For this, gingival tissues from young (4 mo) and aged (24 mo) male and female mice were collected and analyzed by flow cytometry. Cell suspensions were stimulated and stained with eFluor450 (cell viability), anti-CD45 (hematopoietic cells), anti-CD3 (lymphocytes), anti-TCRγδ (γδT cells), anti-IL-15rα (cell proliferation), and anti-Notch-3 (senescence marker). Detection of intracellular cytokines IL-17A and interferon γ (IFNγ) was performed. Gingival expression of specific γ- and δ-chains and cytokines was evaluated by quantitative reverse transcription polymerase chain reaction. A significantly higher number of IL-17A-producing γδT cells and IL-17A expression levels were observed in gingival tissues from aged females but not males. Similarly, the number of gingival Notch-3+ γδT cells increased with aging only in females. IL-15rα was not detected in gingival γδT cells. Chains γ1, 2, 4, 5, 6, and 7 as well as δ1, 2, 4, and 6 were detected. Detection levels of all γ chains except γ1 as well as δ1 and δ2 changed with aging in males, females, or both. Interestingly, number of IL-17A-producing conventional T cells similarly increased with aging only in females. Both sexes showed increased IFNγ+ conventional T-cell numbers with aging; however, it reached significance only in females. In conclusion, the number of gingival IL-17A-producing γδT cells and IL-17A expression increase naturally with aging specifically in females. This sexual dimorphism in gingival γδT and conventional Th17 cell numbers and phenotypes suggests distinct aging-related mechanisms of periodontitis in males and females.

Effects of repeated 3,4-methylenedioxymethamphetamine administration on neurotransmitter efflux and sensory-evoked discharge in the ventral posterior medial thalamus.

3,4-Methylenedioxymethamphetamine (MDMA) is known to enhance tactile sensory perception, an effect that contributes to its popularity as a recreational drug. The neurophysiological basis for the effects of MDMA on somatosensation are unknown. However, MDMA interactions with the serotonin transporter (SERT) and subsequent enhancement of serotonin neurotransmission are well known. The rat trigeminal somatosensory system receives serotonergic afferents from the dorsal raphe nucleus. Because these fibers express SERT, they should be vulnerable to MDMA-induced effects. We found that administration of a challenge injection of MDMA (3 mg/kg i.p.) after repeated MDMA treatment (3 mg/kg per day for 4 days) elicits both serotonin and norepinephrine efflux in the ventral posterior medial (VPM) thalamus of Long-Evans hooded rats, the main relay along the lemniscal portion of the rodent trigeminal somatosensory pathway. We evaluated the potential for repeated MDMA administration to modulate whisker-evoked discharge of individual neurons in this region. After surgically implanting stainless steel eight-wire multichannel electrode bundles, we recorded spike train activity of single cells while activating the whisker pathway using a piezoelectric mechanical stimulator. We found that repeated MDMA administration increased the spontaneous firing rate but reduced both the magnitude and duration of whisker-evoked discharge in individual VPM thalamic neurons. The time course of drug action on neuronal firing patterns was generally consistent with fluctuations in neurotransmitter efflux as shown from our microdialysis studies. On the basis of these results, we propose that single use and repeated administration of MDMA may "distort," rather than enhance, tactile experiences in humans, in part, by disrupting normal spike firing patterns through somatosensory thalamic relay circuits.

Dose-Response Association of Tai Chi and Cognition among Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis.

Previous studies indicated that Tai Chi might be an effective way to improve or prevent cognitive impairments in older populations. However, existing research does not provide clear recommendations about the optimal dose of Tai Chi practice, which is the most effective in improving cognitive function in older adults. The purpose of this systematic review and meta-analysis was to investigate the dose-response relationship between Tai Chi and cognition in community-dwelling older adults. A total of 16 studies with 1121 subjects were included in this study. Meta-regression analyses of Tai Chi duration (Tai Chi session duration, Tai Chi practice duration per week, study duration, and Tai Chi practice duration for the entire study) on the study effect size (ES) were performed to examine the dose-response association of Tai Chi and cognition. The results showed that there was a positive effect of Tai Chi on cognitive function, but there were no statistically significant dose duration effects on cognition. The findings suggest that Tai Chi has beneficial effects on cognitive function, but a longer duration was not associated with larger effects. In order to establish evidence-based clinical interventions using Tai Chi, future research should clearly demonstrate intervention protocol, particularly the style and intensity of Tai Chi.

Pre-Flight Calibration of the Mars 2020 Rover Mastcam Zoom (Mastcam-Z) Multispectral, Stereoscopic Imager.

The NASA Perseverance rover Mast Camera Zoom (Mastcam-Z) system is a pair of zoomable, focusable, multi-spectral, and color charge-coupled device (CCD) cameras mounted on top of a 1.7 m Remote Sensing Mast, along with associated electronics and two calibration targets. The cameras contain identical optical assemblies that can range in focal length from 26 mm ( 25.5 ∘ × 19.1 ∘ FOV ) to 110 mm ( 6.2 ∘ × 4.2 ∘ FOV ) and will acquire data at pixel scales of 148-540 µm at a range of 2 m and 7.4-27 cm at 1 km. The cameras are mounted on the rover's mast with a stereo baseline of 24.3 ± 0.1  cm and a toe-in angle of 1.17 ± 0.03 ∘ (per camera). Each camera uses a Kodak KAI-2020 CCD with 1600 × 1200 active pixels and an 8 position filter wheel that contains an IR-cutoff filter for color imaging through the detectors' Bayer-pattern filters, a neutral density (ND) solar filter for imaging the sun, and 6 narrow-band geology filters (16 total filters). An associated Digital Electronics Assembly provides command data interfaces to the rover, 11-to-8 bit companding, and JPEG compression capabilities. Herein, we describe pre-flight calibration of the Mastcam-Z instrument and characterize its radiometric and geometric behavior. Between April 26 t h and May 9 t h , 2019, ∼45,000 images were acquired during stand-alone calibration at Malin Space Science Systems (MSSS) in San Diego, CA. Additional data were acquired during Assembly Test and Launch Operations (ATLO) at the Jet Propulsion Laboratory and Kennedy Space Center. Results of the radiometric calibration validate a 5% absolute radiometric accuracy when using camera state parameters investigated during testing. When observing using camera state parameters not interrogated during calibration (e.g., non-canonical zoom positions), we conservatively estimate the absolute uncertainty to be < 10 % . Image quality, measured via the amplitude of the Modulation Transfer Function (MTF) at Nyquist sampling (0.35 line pairs per pixel), shows MTF Nyquist = 0.26 - 0.50 across all zoom, focus, and filter positions, exceeding the > 0.2 design requirement. We discuss lessons learned from calibration and suggest tactical strategies that will optimize the quality of science data acquired during operation at Mars. While most results matched expectations, some surprises were discovered, such as a strong wavelength and temperature dependence on the radiometric coefficients and a scene-dependent dynamic component to the zero-exposure bias frames. Calibration results and derived accuracies were validated using a Geoboard target consisting of well-characterized geologic samples. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11214-021-00795-x.

Direct coupling of marine invertebrate spawning with phytoplankton blooms.

Spawning of green sea urchins and blue mussels may be triggered by a heat-stable metabolite released by various species of phytoplankton. Mussels require a higher phytoplankton density for a maximum response than urchins, perhaps because mussels are exposed to higher concentrations of phytoplankton as a result of their filtering activity. Phytoplankton as a spawning cue appears to integrate numerous physical and biotic factors indicating favorable conditions for larval growth and survival. Evolution of similar direct coupling of the larval phase with phytoplankton blooms may be common among marine invertebrates.

MDMA (3,4-methylenedioxymethamphetamine)-mediated distortion of somatosensory signal transmission and neurotransmitter efflux in the ventral posterior medial thalamus.

MDMA (3,4-methylenedioxymethamphetamine, Ecstasy) is reported to enhance tactile sensory perception, an effect that is believed to contribute to its popularity as a recreational drug. To date, no literature exists that addresses the neurophysiological mechanisms underlying the effects of MDMA on somatosensation. However, MDMA interactions with the serotonin transporter protein (SERT) are well known. The rat trigeminal somatosensory system has been studied extensively and receives serotonergic afferents from the dorsal raphe nucleus. Given that these fibers express SERT, they should be vulnerable to MDMA-induced effects. We found that short-term low-dose MDMA administration (3 mg/kg i.p.) led to a significant increase in 5-hydroxytryptamine (5-HT) efflux in the ventral posterior medial (VPM) thalamus, the main relay along the lemniscal portion of the rodent trigeminal somatosensory pathway. We further evaluated the potential for MDMA to modulate whisker-evoked discharge (WED) of individual neurons in this region. After surgically implanting stainless steel 8-wire multichannel electrode bundles, we recorded spike train activity from single cells of halothane-anesthetized rats while mechanically activating the whisker pathway. We found that short-term low-dose MDMA (3 mg/kg i.p.) increased the spontaneous firing rate but reduced the magnitude and duration of WED in individual VPM thalamic neurons. It is noteworthy that the time course of drug action on neuronal firing patterns was generally consistent with increased 5-HT efflux as shown from our microdialysis studies. Based on these results, we propose the working hypothesis that MDMA may "distort" rather than enhance tactile experiences in humans, in part, by disrupting normal spike firing patterns through somatosensory thalamic relay circuits.

Cryptococcus gattii infections on Vancouver Island, British Columbia, Canada: emergence of a tropical fungus in a temperate environment.

BACKGROUND: Cryptococcus gattii causes disease among immunocompetent individuals in the tropics and subtropics. We document the appearance of C. gattii infections on Vancouver Island (VI), a temperate region, and discuss reasons for this emergence. METHODS: Data on Cryptococcus hospitalizations for the calendar years 1995 through 2004 were reviewed. Viable historic isolates stored at the provincial public health laboratory between 1987 and 2000 were serotyped. Human cases were mapped by place of residence. RESULTS: Cryptococcosis among HIV negative individuals diagnosed on VI increased sharply after 1999. C. gattii was not detected in stored isolates prior to 1999. C. gattii cases lived in a specific biogeoclimatic zone on VI. Higher rates of illness were associated with exposure to the central region of VI. CONCLUSIONS: The emergence of C. gattii in a temperate region is unprecedented. Clinicians should consider C. gattii in the differential diagnosis of individuals who travelled to certain areas in British Columbia.

Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor.

BACKGROUND: Vav is a guanine-nucleotide exchange factor for the Rho-like small GTPases RhoA, Rac1 and Cdc42, which regulate cytoskeletal reorganization and activation of stress-activated protein kinases (SAPK/JNKs). Vav is expressed in hematopoietic cells and is phosphorylated in T and B cells following activation of various growth factor or antigen receptors. Vav interacts with several signaling molecules in T cells, but the functional relevance of these interactions is established only for Slp76: they cooperate to induce activity of the transcription factor NF-AT and interleukin-2 expression. We have investigated the role of Vav in T cells by generating vav-/- mice. RESULTS: Mice deficient for vav were viable and healthy, but had impaired T-cell development. In vav-/- T cells, in response to activation of the T-cell receptor (TCR), cell cycle progression, induction of NF-ATc1 activity, downregulation of the cell-cycle inhibitor p27Kip1, interleukin-2 production, actin polymerization and the clustering of TCRs into patches and caps--a cytoskeletal reorganization process--were defective. TCR-mediated activation of mitogen-activated protein kinase and SAPK/JNK was unaffected. Ca2+ mobilization was impaired in vav-/- thymocytes and T cells. In wild-type cells, Vav constitutively associated with the cytoskeletal membrane anchors talin and vinculin. In the absence of Vav, phosphorylation of Slp76, Slp76-talin interactions, and recruitment of the actin cytoskeleton to the CD3 zeta chain of the TCR co-receptor were impaired. CONCLUSIONS: Vav is a crucial regulator of TCR-mediated Ca2+ flux, cytoskeletal reorganization and TCR clustering, and these are required for T-cell maturation, interleukin-2 production and cell cycle progression.

Real vs simulated umbilical cords for emergency umbilical catheterization training: a randomized crossover study.

OBJECTIVE: To measure performance, fidelity and preference of two emergency umbilical vessel catheter (eUVC) simulation models. STUDY DESIGN: A randomized crossover trial of senior pediatric residents randomized to place an eUVC first using a real cord (RC) or simulated cord (SC), and then place an eUVC using the other model. The eUVC placement times were recorded and analyzed. Subjects rated physical and functional fidelity and preference for each model. RESULTS: The eUVC placement time (mean±s.d. s) was slower in RC vs SC (153 s ±71 vs 88 s ±35, P<0.001), however, there was no difference in eUVC placement time in the group that worked with SC first (115 s ±36 vs 97 s ±35, P=0.161). Physical and functional fidelity of RC were rated higher than SC (P<0.001), and RC were preferred. CONCLUSION: RC has higher physical and functional fidelity, and are preferred for training by pediatric residents, despite longer placement times.

p-Type transition-metal doping of large-area MoS2 thin films grown by chemical vapor deposition.

Two-dimensional transition metal dichalcogenides (e.g. MoS2) have recently emerged as a promising material system for electronic and optoelectronic applications. A major challenge for these materials, however, is to realize bipolar electrical transport properties (i.e. both p-type and n-type conduction), which is critical for enhancing device performance and functionalities. Here, we demonstrate the transition metal zinc as a p-type dopant in the otherwise n-type MoS2, through systematic characterizations of large area Zn-doped MoS2 thin films grown by a one-step chemical vapor deposition (CVD) approach. Raman characterization and X-ray photoelectron spectroscopy studies identified millimeter-scale, monolayer films with 1-2% Zn as dopants. Zinc doping suppresses n-type conductivity in MoS2 and shifts its Fermi level downwards. The stability and p-type nature of Zn dopants were further confirmed by density-functional-theory calculations of formation energies and electronic band structures. The electrical transport properties of Zn-MoS2 films can be influenced by stoichiometry, and p-type gate transfer characteristics were realized by thermal treatment under a sulfur atmosphere. Our work highlights transition-metal doping followed by sulfur vacancy elimination in CVD grown films as a promising route for achieving large area p-type transition metal dichalcogenide films that are essential for practical applications in electronics and optoelectronics.

Epitaxial thin films of pyrochlore iridate Bi2+xIr2-yO7-δ: structure, defects and transport properties.

While pyrochlore iridate thin films are theoretically predicted to possess a variety of emergent topological properties, experimental verification of these predictions can be obstructed by the challenge in thin film growth. Here we report on the pulsed laser deposition and characterization of thin films of a representative pyrochlore compound Bi2Ir2O7. The films were epitaxially grown on yttria-stabilized zirconia substrates and have lattice constants that are a few percent larger than that of the bulk single crystals. The film composition shows a strong dependence on the oxygen partial pressure. Density-functional-theory calculations indicate the existence of BiIr antisite defects, qualitatively consistent with the high Bi: Ir ratio found in the films. Both Ir and Bi have oxidation states that are lower than their nominal values, suggesting the existence of oxygen deficiency. The iridate thin films show a variety of intriguing transport characteristics, including multiple charge carriers, logarithmic dependence of resistance on temperature, antilocalization corrections to conductance due to spin-orbit interactions, and linear positive magnetoresistance.

Clinical Decision Support Systems and Prevention: A Community Guide Cardiovascular Disease Systematic Review.

CONTEXT: Clinical decision support systems (CDSSs) can help clinicians assess cardiovascular disease (CVD) risk and manage CVD risk factors by providing tailored assessments and treatment recommendations based on individual patient data. The goal of this systematic review was to examine the effectiveness of CDSSs in improving screening for CVD risk factors, practices for CVD-related preventive care services such as clinical tests and prescribed treatments, and management of CVD risk factors. EVIDENCE ACQUISITION: An existing systematic review (search period, January 1975-January 2011) of CDSSs for any condition was initially identified. Studies of CDSSs that focused on CVD prevention in that review were combined with studies identified through an updated search (January 2011-October 2012). Data analysis was conducted in 2013. EVIDENCE SYNTHESIS: A total of 45 studies qualified for inclusion in the review. Improvements were seen for recommended screening and other preventive care services completed by clinicians, recommended clinical tests completed by clinicians, and recommended treatments prescribed by clinicians (median increases of 3.8, 4.0, and 2.0 percentage points, respectively). Results were inconsistent for changes in CVD risk factors such as systolic and diastolic blood pressure, total and low-density lipoprotein cholesterol, and hemoglobin A1C levels. CONCLUSIONS: CDSSs are effective in improving clinician practices related to screening and other preventive care services, clinical tests, and treatments. However, more evidence is needed from implementation of CDSSs within the broad context of comprehensive service delivery aimed at reducing CVD risk and CVD-related morbidity and mortality.

Dopamine and glutamate control each other's release in the basal ganglia: a microdialysis study of the entopeduncular nucleus and substantia nigra.

This study utilized microdialysis in conscious rats to investigate dopaminergic control of excitatory amino acid release in the entopeduncular nucleus (EPN), and glutamatergic control of dopamine release in the substantia nigra pars reticulata (SNr). EPN dialysates contained both glutamate and aspartate, which were elevated by dopamine depletion with reserpine and 6-hydroxydopamine (6-OHDA), reduced by the D2/3 agonist LY 171555 and unaffected by the D1 agonist SKF 38393, in line with current theory. The D2/3 agonist RU 24213 was behaviourally active but paradoxically increased glutamate and aspartate release in EPN, possibly via kappa opioid receptor blockade. 6-OHDA-hemilesioned rats also showed a significant increase in glutamate and aspartate contralaterally, suggesting that nigrostriatal dopamine affects EPN neurotransmission bilaterally. In reserpine-treated rats, basal levels of dopamine in the SNr were greatly reduced, and were further lowered by focal application of NMDA antagonists, suggestive of the removal of a high glutamatergic tone. A threshold amount of L-DOPA applied to the SNr elevated dopamine output about two-fold and 5-HT output about 13-fold, indicating L-DOPA effects the release of monoamines other than dopamine. Concomitant addition of the NMDA antagonists potentiated these releases synergistically, suggesting that this could be how they facilitate the antiparkinsonian action of L-DOPA.

Stimulation of basal and L-DOPA-induced motor activity by glutamate antagonists in animal models of Parkinson's disease.

In parkinsonism, glutamate pathways within the basal ganglia become overactive, leading to the suggestion that glutamate antagonists might possess antiparkinsonian qualities. This report examines the motor properties of antagonists of NMDA and AMPA-type glutamate receptors, as well as some inhibitors of glutamate release, in animal models of idiopathic Parkinson's disease. High affinity NMDA open-channel blockers (e.g. MK 801, phencyclidine), are highly potent antagonists with inconsistent antiakinetic and strong myorelaxant activity. Other compounds are better tolerated and are capable of relieving immobility and muscular rigidity by themselves (e.g. 1-aminoadamantanes, polyamine site antagonists, kappa agonists, riluzole). Yet others do not restore movements alone (e.g. dextromethorphan, ketamine), but may interact with and strengthen the antiparkinsonian action of L-DOPA (e.g. competitive NMDA and AMPA antagonists, lamotrigine). They may do this by potentiating dopaminergic behaviours mediated by D1 or D2 receptors, or by some other mechanism.

A controlled study of diffuse idiopathic skeletal hyperostosis. Clinical features and functional status.

Diffuse idiopathic skeletal hyperostosis (DISH) is a common but little-studied disorder in the elderly that is infrequently recognized by physicians. Its prevalence in adults over 40 years of age is estimated at 3.8% for men and 2.6% for women. The present case-control study evaluated the history of pain and stiffness, radicular pain and enthesitis, physical findings on the musculoskeletal examination, and level of physical and psychologic disability in 130 persons: 56 patients with DISH, 43 control patients with spondylosis of the lumbar spine, and 31 healthy control patients. DISH patients were more likely to report a past history of upper extremity pain, medial epicondylitis of the elbow, enthesitis of the patella or heel, or dysphagia than spondylosis patients. They had more extremity and spinal stiffness and pain than healthy controls. DISH patients weighed more at a young age and their body mass index was greater at the time of the clinical evaluation than either spondylosis or healthy control patients. On musculoskeletal examination, DISH patients had a greater reduction in neck rotation and thoracic movements than either spondylosis patients or healthy controls, and had a greater reduction in lumbar movement than healthy controls. DISH patients had similar levels of spinal disability and physical disability overall, as measured by standardized indices, as spondylosis patients. No differences were found among the 3 groups of patients for the laboratory tests evaluated. DISH is clearly a distinct disorder with signs and symptoms that distinguish it from other causes of spinal complaint and from healthy individuals. It has the potential to cause major disability. Future studies need to address the natural history of DISH, pursue pathogenic mechanisms, and evaluate treatment modalities.

Differential effects of dopamine D1 and D2 agonists and antagonists on velocity of movement, rearing and grooming in the mouse. Implications for the roles of D1 and D2 receptors.

A system combining visual recording of rearing and grooming, with automatic measurement of slow and fast components of locomotion, was examined for its suitability as a means of studying the effects on behaviour of conventional and novel dopaminergic drugs in the mouse. Amphetamine (0.1-10 mg/kg) selectively stimulated fast movements and affected rearing bimodally. Apomorphine (0.01-5 mg/kg) influenced locomotion polyphasically, depressing fast movements and enhancing slow ones, and producing parallel changes in rearing. Both drugs reduced grooming monotonically. A dose of apomorphine (25 micrograms/kg) which is considered to act presynaptically produced haloperidol-resistant sedation, while a larger dose (0.5 mg/kg; with postsynaptic actions) evoked head-down sniffing and ponderous walking that were partially prevented by pretreatment with 0.05 mg/kg haloperidol (D2 blocker), but not 0.01 mg/kg SCH 23390 (D1 blocker). The behavioural effects of haloperidol (0.2-0.4 mg/kg) and SCH 23390 (0.05 mg/kg) were indistinguishable; both drugs caused sedation and inhibited all forms of motor activity. Small doses of SCH 23390 (2-10 micrograms/kg) and large doses of the D1 agonist SKF 38393 (3-10 mg/kg) evoked excessive grooming. The drug SKF 38393 (1-30 mg/kg) had no other effects on motor behaviour, whereas the whole spectrum of pre- and postsynaptic motor responses produced by apomorphine could be duplicated with the D2 agonist RU 24213 (0.05-15 mg/kg). The differential sensitivity of fast and slow components of locomotion to treatment with drug suggests these are qualitatively distinct responses. The results implicate D2 receptors in the mechanisms of locomotion and rearing, and D1 receptors in the expression of grooming.

Behavioural interactions involving D1 and D2 dopamine receptors in non-habituated mice.

The effects of SKF 38393 (D1-agonist) and SCH 23390 (D1-antagonist) were compared with those of haloperidol (D2 greater than D1-antagonist) and metoclopramide (D2-antagonist) in the absence or presence of apomorphine (D1/D2-agonist) and RU 24213 (D2 agonist) in non-habituated mice. The motor behaviour studied which was typical of the species included sniffing, grooming, rearing and locomotion. Apomorphine and RU 24213 induced frozen inactivity, in small doses and head-down sniffing, coupled with ponderous forward walking, in large doses, consistent with the stimulation of D2 receptors at pre- and postsynaptic sites, respectively. Neither SKF 38393 nor metoclopramide modified rearing or locomotion over a wide range of doses. SKF 38393 promoted sniffing and grooming, while metoclopramide suppressed this behaviour. Apart from increased grooming with SCH 23390 in small doses, both this drug and haloperidol dose-dependently decreased all motor activity. In combination studies, the D2 blockers reversed the effects of stimulation of D2 receptors and released normal behaviour, whereas SCH 23390 converted both the behavioural syndromes mediated by pre- and postsynaptic D2-receptors into severe inactivity (but not catalepsy). The drug SKF 38393 had the opposite effect and promoted motor responding in the presence of D2 stimulation, in doses that were otherwise ineffective by themselves. In this model, SCH 23390 modified behaviour mediated by D2-receptors in a different manner to the D2-receptor antagonists, haloperidol and metoclopramide, suggesting it may interact with a different population of D2-receptors, or with D1-receptors. These and earlier data can be interpreted to mean that both subclasses of the dopamine receptor have distinct and probably interdependent roles in the management of motor behaviour.

Regional changes in brain dopamine utilization during status epilepticus in the rat induced by systemic pilocarpine and intrahippocampal carbachol.

Systemic administration of pilocarpine (400 mg/kg i.p.) or intrahippocampal injection of carbachol (100 micrograms/1 microliters) induced limbic motor seizures in rats, characterized by head weaving and paw treading, rearing and falling, and forepaw myoclonus, developing into status epilepticus. After being in status for 30 min, rats were killed and levels of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined in eight brain regions by high performance liquid chromatography. Pilocarpine-induced seizures significantly elevated dopamine in the striatum, and in both dorsal and ventral aspects of the hippocampus, but did not affect dopamine in substantia nigra, nucleus accumbens, olfactory tubercle, cingulate cortex or amygdala. Metabolite levels were increased in striatum, substantia, nigra, nucleus accumbens and cingulate cortex, and fell in the hippocampus, but remained unchanged in the olfactory tubercle and amygdala. Intrahippocampal carbachol significantly raised the dopamine contents of striatum and nigra, and in both ventral and dorsal aspects of the hippocampus, but not elsewhere. DOPAC and/or HVA were elevated in all brain regions tested, save for amygdala and dorsal hippocampus. These changes translated into seizure-induced increases in dopamine utilization in the nucleus accumbens, olfactory tubercle and cingulate cortex, and to a fall in dopamine utilisation in the hippocampus, with no net change in amygdala. In addition pilocarpine (but not carbachol) increased dopamine utilization in the nigrostriatal axis, possibly through a seizure-unrelated mechanism. The relevance of these findings to seizure development are discussed.