Chronic intermittent ethanol exposure during adolescence: Effects on social behavior and ethanol sensitivity in adulthood

This study assessed long-lasting consequences of repeated ethanol exposure during two different periods of adolescence on 1) baseline levels of social investigation, play fighting, and social preference and 2) sensitivity to the social consequences of acute ethanol challenge. Adult male and female Sprague-Dawley rats were tested 25 days after repeated exposure to ethanol (3.5 g/kg intragastrically [i.g.], every other day for a total of 11 exposures) in a modified social interaction test. Early-mid adolescent intermittent exposure (e-AIE) occurred between postnatal days (P) 25 and 45, whereas late adolescent intermittent exposure (l-AIE) was conducted between P45 and P65. Significant decreases in social investigation and social preference were evident in adult male rats, but not their female counterparts following e-AIE, whereas neither males nor females demonstrated these alterations following l-AIE. In contrast, both e-AIE and l-AIE produced alterations in sensitivity to acute ethanol challenge in males tested 25 days after adolescent exposure. Ethanol-induced facilitation of social investigation and play fighting, reminiscent of that normally seen during adolescence, was evident in adult males after e-AIE, whereas control males showed an age-typical inhibition of social behavior. Males after l-AIE were found to be insensitive to the socially suppressing effects of acute ethanol challenge, suggesting the development of chronic tolerance in these animals. In contrast, females showed little evidence for alterations in sensitivity to acute ethanol challenge following either early or late AIE. The results of the present study demonstrate a particular vulnerability of young adolescent males to long-lasting detrimental effects of repeated ethanol. Retention of adolescent-typical sensitivity to the socially facilitating effects of ethanol could potentially make ethanol especially appealing to these males, therefore promoting relatively high levels of ethanol intake later in life.     

Interactions among paired-pulse facilitation and post-tetanic and long-term potentiation in the mossy fiber-CA3 pathway in rat hippocampus

Long-term potentiation (LTP) observed at the synapses of mossy fiber-CA3(MF-CA3) pathway differs from that observed at the Schaffer collateral-CA1 pathway (SC-CA1), in being independent of N-methyl-D-aspartate (NMDA) receptors. The induction and expression mechanisms of MF-CA3 LTP remain to be determined. We have compared the occurrence and magnitude of LTP with that of two other indicators of presynaptic plasticity, post-tetanic potentiation (PTP) and paired-pulse facilitation in control brain slices from young rats and in slices treated with phorbol-12, 13-diacetate (PDAc), a protein kinase C activator. Paired-pulse facilitation is a potentiation of the second of two responses at intervals of tens of milliseconds and is due to a presynaptic calcium increase. Tetanic stimulation of mossy fibers induced LTP is area CA3 in only 64% of slices. In those slices that showed LTP, the size of the PIP was significantly greater than in those slices that did not, and the degree of correlation between LTP and PTP amplitude overall was r = 0.7. The degree of paired-pulse facilitation before tetanic stimulation was also positively correlated to the occurrence and magnitude of LTP and PTP after tetanic stimulation. The correlation coefficient between PTP and PPF was 0.749 for all slices studied, while that between LTP and PPF was 0.835 overall. Application of PDAc potentiated synaptic transmission and abolished paired-pulse facilitation (control ratio of second to first response, 2.1; after PDAc ratio 0.8) and LTP. PTP was absent at the control stimulus intensity in PDAc, but was apparent if the stimulus intensity was reduced to give a response of the same amplitude as before administration of PDAc. Stable LTP was also accompanied by a marked decrease in paired-pulse facilitation. These data suggest that MF-CA3 LTP, PTP and paired-pulse facilitation share common mechanisms and are all at least primarily of presynaptic origin. The occurrence of large paired-pulse facilitation or PTP is a predictor of a preparation which will show LTP. It is likely that presynaptic [Ca^2-], is an essential factor in LTP, PTP and paired-pulse facilitation, as well as the potentiation induced by application of PDAc, but the factors which determine whether or not [Ca^2-], rises following these various stimuli are not clear from the techniques used in these investigations. © 1996 Wiley-Liss, Inc.     

Advancing Pharmacological Treatments for Opioid Use Disorder (ADaPT-OUD): an Implementation Trial in Eight Veterans Health Administration Facilities

BackgroundIdentifying effective strategies to improve access to medication treatments for opioid use disorder (MOUD) is imperative. Within the Veterans Health Administration (VHA), provision of MOUD varies significantly, requiring development and testing of implementation strategies that target facilities with low provision of MOUD.ObjectiveDetermine the effectiveness of external facilitation in increasing the provision of MOUD among VHA facilities with low baseline provision of MOUD compared to matched controls.DesignPre-post, block randomized study designed to compare facility-level outcomes in a stratified sample of eligible facilities. Four blocks (two intervention facilities in each) were defined by median splits of both the ratio of patients with OUD receiving MOUD and number of patients with OUD not currently receiving MOUD (i.e., number of actionable patients). Intervention facilities participated in a 12-month implementation intervention.ParticipantsVHA facilities in the lowest quartile of MOUD provision (35 facilities), eight of which were randomly assigned to participate in the intervention (two per block) with twenty-seven serving as matched controls by block.InterventionExternal facilitation included assessment of local barriers/facilitators, formation of a local implementation team, a site visit for action planning and training/education, cross-facility quarterly calls, monthly coaching calls, and consultation.Main MeasuresPre- to post-change in the facility-level ratio of patients with an OUD diagnosis receiving MOUD compared to control facilities.Key ResultsIntervention facilities significantly increased the ratio of patients with OUD receiving MOUD from an average of 18% at baseline to 30% 1 year later, with an absolute difference of 12% (95% confidence interval [CI]: 6.6%, 17.0%). The difference in differences between intervention and control facilities was 3.0% (95% CI: − 0.2%. 6.7%). The impact of the intervention varied by block, with smaller, less complex facilities more likely to outperform matched controls.ConclusionsIntensive external facilitation improved the adoption of MOUD in most low-performing facilities and may enhance adoption beyond other interventions less tailored to individual facility contexts.     

Interneuronal networks mediate cortical inhibition and facilitation

ObjectiveRecruitment of interneuronal circuits generating later indirect (I) waves seem to be important in short-interval intracortical inhibition (SICI) and facilitation (SICF) development. This study assessed whether individual variations in intracortical inhibition and facilitation could be explained by variation in recruitment of interneuronal networks.MethodsCortical excitability was assessed using a figure of eight coil, with motor evoked responses recorded over the contralateral abductor pollicis brevis (APB) muscle. I-wave recruitment was inferred from the measurement of motor evoked potential (MEP) onset latencies, with coil positioned in posterior-to-anterior (early I waves) and anterior-to-posterior (later I waves) directions.ResultsSubtle variability in the recruitment of later I-waves (I3) was evident across subjects. Importantly, mean SICI (P < 0.05) was significantly greater in subjects recruiting I3 waves, as were the two SICI peaks at interstimulus intervals of 1 ms (P < 0.05) and 3 ms (P < 0.05). In addition, mean SICF was significantly greater in participants exhibiting an AP-to-LM latency differences of <4 ms (P < 0.01). There was no significant correlation between I-wave recruitment and intracortical facilitation, motor evoked potential amplitude or cortical silent period duration.ConclusionsDifferential recruitment of interneuronal networks appears to underlie the generation and individual variations in intracortical inhibition and facilitation.SignificanceInvestigating cortical interneuronal networks in human diseases may yield novel pathophysiological insights.     

Differential labeling of the vestibular complex following unilateral injections of horseradish peroxidase into the cat and rat locus coeruleus

In anaesthetized cats, lumbar dorsal horn neurons were excited by brief noxious radiant heating of glabrous hindpaw skin. These nociceptive responses were inhibited by concomitant repetitive electrical stimulation of the ipsilateral deep radial nerve. Noxious heat responses were linearly correlated with skin temperature during heating. The slope of this stimulus-response function was decreased, and the response threshold increased, by deep radial nerve stimulation. Microinjection of lidocaine into the medullary raphe attenuated the inhibition induced by deep radial nerve stimulation. The results indicate that in the cat, ‘diffuse noxious inhibitory controls’ (DNIC) involve medial medullary regions.     

Inhibition of the responses of cat dorsal horn neurons to noxious skin heating by stimulation in medial or lateral medullary reticular formation

Summary Responses of single lumbar dorsal horn units to noxious radiant heating (50° C, 10 s) of glabrous footpad skin were recorded in cats anesthetized with sodium pentobarbital and 70% nitrous oxide. The heat-evoked responses of 37/40 units were reduced during electrical stimulation (100 ms trains, 100 Hz, 3/s, 25–600 A) in the medullary nucleus raphe magnus (NRM) and/or in laterally adjacent regions of the medullary reticular formation (MRF). Inhibition was elicited by stimulation in widespread areas of the medulla, but with greatest efficacy at ventrolateral sites. The magnitude of inhibition increased with graded increases in medullary stimulation intensity. Mean current intensities at threshold for inhibition or to produce 50% inhibition were higher for NRM than for MRF sites. Units' responses to graded noxious heat stimuli increased linearly from threshold (42–43° C) to 52° C. During NRM (5 units) or ipsilateral MRF stimulation (7 units), responses were inhibited such that the mean temperature-response functions were shifted toward higher temperatures with increased thresholds (1.5° and 1° C, respectively) and reduced slopes (to 60% of control). Contralateral MRF stimulation had a similar effect in 4 units. Inhibitory effects of NRM and MRF stimulation were reduced (by >25%) or abolished in 4/6 and 5/12 units, respectively, following systemic administration of the serotonin antagonist methysergide. Inhibitory effects from NRM, ipsi- and contralateral MRF were reduced or abolished in 2/9, 4/8 and 6/9 cases, respectively, following systemic administration of the noradrenergic antagonist phentolamine. These results confirm and extend previous studies of medullospinal inhibition and the role of monoamines, and are discussed in terms of analgesic mechanisms.     

移动式平板训练对脑卒中偏瘫患者的运动功能及日常生活活动能力的影响

目的：观察移动式平板训练对脑卒中偏瘫患者本体感觉障碍的运动能力及日常生活活动能力的影响。方法：脑卒中偏瘫患者30例随机分为观察组和对照组各15例,2组患者均给予常规药物治疗及康复训练,观察组加用移动式平板训练进行本体感觉训练,对照组加用神经肌肉本体感觉促进疗法（PNF）进行治疗。治疗前后采用Tecnobody本体感觉评估系统（ATE及Time值）、Fugl-Meyer下肢运动功能评定量表（FMA）、Berg平衡量表（BBS）、改良Barthel指数评定表（MBI）评估2组患者的本体感觉、下肢运动功能、平衡能力及日常生活活动能力。 结果：治疗8周后,2组ATE值及Time值均较治疗前明显降低（P<0.05）,且观察组更低于对照组（P<0.05）;2组FMA、BBS、MBI评分均较治疗前明显提高（P<0.05）,且观察组FMA评分较对照组明显提高（P<0.05）,但BBS、MBI评分2组间比较差异无统计学意义。结论：移动式平板训练对脑卒中偏瘫患者本体感觉及下肢运动功能的疗效优于PNF疗法;对于平衡能力及日常生活活动能力的改善,两者未见明显区别。     

神经肌肉关节促进法对脑梗死偏瘫患者下肢肌张力的影响

目的 探讨神经肌肉关节促进法（NJF）对脑梗死偏瘫患者下肢肌张力的治疗作用及效果。方法 收集脑梗死患者136例,根据是否使用NJF治疗分为治疗组（66例）与对照组（70例）。分别在治疗前、治疗10 d后采用改良Ashworth量表评定2组患者偏瘫侧的下肢肌张力,Brunnstrom分期评定2组患者偏瘫侧下肢运动功能,根据转移时所需帮助量的程度评定患者的转移能力（包括卧坐转移、坐站转移）,Bobath法平衡功能评定患者平衡能力,Holden功能性步行量表评定患者步行能力。结果 治疗10 d后治疗组患者下肢高肌张力降低比例为21.2%,高于对照组的1.4%(P <0.001);治疗组患者坐站转移能力好转比例为47.0%,高于对照组的27.1%(P <0.05)。结论 NJF治疗有利于降低脑梗死偏瘫患者下肢的高肌张力,使其趋于正常水平,有助提高其坐站转移能力。