Effects Of Lorazepam Research Articles

Effects of lorazepam on saccadic eye movements - evidence from prosaccade and free viewing tasks.

Peak velocities of saccadic eye movements are reduced after benzodiazepine administration. Even though this is an established effect, past research has only examined it in horizontal prosaccade tasks. The spectrum of saccadic eye movements, however, is much larger. Therefore, we aimed to make a first attempt at filling this research gap by testing benzodiazepine effects on saccades under different experimental task conditions. 1mg lorazepam or placebo was administered (within-subjects, double-blind, in randomised order) to n = 30 healthy adults. Participants performed an extended version of the prosaccade task, including vertical saccade directions and different stimulus eccentricities, as well as a free viewing task. Results from the prosaccade task confirmed established effects of benzodiazepines as well as saccade direction on saccadic parameters but additionally showed that the drug effect on peak velocity was independent of saccade direction. Remarkably, in the free viewing task peak velocities as well as other saccade parameters were unaffected by lorazepam. Furthermore, exploration patterns during free viewing did not change under lorazepam. Overall, our findings further consolidate the peak velocity of prosaccades as a biomarker of sedation. Additionally, we suggest that sedative effects of low doses of benzodiazepines may be compensated in tasks that more closely resemble natural eye movement behaviour, possibly due to the lack of time constraints or via neurophysiological processes related to volition.

Long-term lorazepam use may be associated with worse long-term outcomes among patients with pancreatic adenocarcinoma

BackgroundLorazepam recently has been reported to alter the tumor microenvironment of pancreatic adenocarcinoma in a murine model. We sought to evaluate whether the use of lorazepam was associated with worse outcomes among patients with pancreatic adenocarcinoma. MethodsMedicare beneficiaries diagnosed with stage I-IV pancreatic adenocarcinoma between 2013 and 2019 were identified from the Surveillance, Epidemiology and End Results-Medicare database. The association of lorazepam prescription relative to overall survival and recurrence-free survival was examined. ResultsAmong 2,810 patients with stage I–III and 10,181 patients with stage IV pancreatic adenocarcinoma, a total of 133 (4.7%) and 444 individuals (4.4%) had a lorazepam prescription before disease diagnosis, respectively. Although the overall lorazepam group had comparable 5-year overall survival (15.0% vs 14.2%, P = .20) and recurrence-free survival (12.7% vs 10.9%, P = .42) with the no-lorazepam group after pancreatic adenocarcinoma resection, individuals with long-term lorazepam prescription (>30 days) had worse 5-year overall survival (9.0% vs 21.0%, P = .02) and recurrence-free survival (6.4% vs 17.1%, P = .009) compared with short-term lorazepam users (≤30 days). Similarly, among patients with metastatic pancreatic adenocarcinoma, individuals with a long-term lorazepam prescription had worse 1-year overall survival (9.7% vs 15.9%, P = .02) compared with patients who had short-term lorazepam prescriptions. On multivariable analysis, long-term lorazepam prescription was independently associated with overall survival among patients with resectable (hazard ratio, 1.82; 95% confidence interval, 1.22–2.74) and metastatic pancreatic adenocarcinoma (hazard ratio, 1.24; 95% confidence interval, 1.02–1.51). ConclusionLong-term lorazepam prescription was associated with worse long-term outcomes among patients who underwent resection for pancreatic adenocarcinoma and patients with metastatic pancreatic adenocarcinoma. These data support the need for further large scale studies to confirm a potential harmful effect of lorazepam among patients with pancreatic adenocarcinoma.

Comparative analysis of the anti-depression effects of lorazepam, acupuncture, and curcumin utilizing the forced swimming test in experimental rats models

Introductionlorazepam is one of benzodiazepine medication that is usually used for its sedative and anxiolytic effect and has anti-depressant like effects. Turmeric is a plant that contain curcumin as main active compound that exert its antidepressant action inhibit monoamine oxidase and increase levels of dopamine and serotonin in brain. Aimthe present study investigate the depression effect of curcumin (natural selective serotonin inhibitors) in comparison with acupuncture and lorazepam. Method32 adult rats weighing (150 g−280 g) were divided equally into 8 groups each group contain 4 rats. The first 3 group of rats were treated with lorazepam, mixture of (curcumin, black pepper and olive oil) and pricked with insulin needle at point gb39, respectively, while second 4 groups of rats were received lorazepam and mixture, lorazepam and acupuncture, mixture and acupuncture, and lorazepam, mixture and acupuncture, separately, and the eighth group is control group don't receive any drugs. After 35 days, forced swimming test was made for all rats. ResultsLiver parameters: - GOT increased in all group, GPT increased in rat's group that received lorazepam, mixture group and lorazepam+ mixture group, This indicates the existence of problems previously with the liver of the rat used, and what remains is the high levels of GOT and GPT in the control group, while TSB is within the normal range for all groups. Kidney parameters:-blood urea levels increased in all groups and S. creatinine levels within normal range for all groups. Conclusionthe evaluation of natural SERMs in the forced swimming test showed promising antidepressant-like effects, comparable to lorazepam and acupuncture. Further research is needed to understand the mechanisms and determine optimal dosage and safety. Natural selective serotonin inhibitors hold potential as alternative or complementary treatments for depression.

Effect of Lorazepam on the Development of the Hairy Maggot Blow Fly, Chrysomya rufifacies (Macquart): Implication for Forensic Entomology.

Entomotoxicology is based on using insect evidence recovered from a dead body to find out the cause and time of the death. Drugs can accumulate in fly larvae when they ingest the flesh of deceased persons and alter the normal development of the fly causing implications in calculating postmortem intervals. Lorazepam is an antidepressant generally used to treat anxiety. Larvae of Chrysomya rufifacies were fed on the beef liver mixed with lorazepam to study the effect of lorazepam on the developmental rate of larvae and to count delay in postmortem interval. Larvae grown on the beef liver with different doses of lorazepam showed delayed development as compared to normal larvae. The life cycle durations in experimental cultures with different concentrations of lorazepam completed in 1 ppm (272.56 hrs), 2 ppm (289.23 hrs), 3 ppm (324.10 hrs), and 4 ppm (350.72 hrs), while in the control culture life cycle completed in 257.26 hrs. The length, weight, and width of the larvae treated with lorazepam were smaller than the untreated culture. Length, weight, and width decreased with increased concentration of lorazepam. This delay in development ultimately affects the postmortem interval. That is why prior knowledge of the life cycle of flies with respect to various drugs needs to be studied, and these baseline data can be used to calculate postmortem interval and cause of death.

Lorazepam in catatonia – Past, present and future of a clinical success story

The effect of lorazepam in the treatment of catatonia is outstanding and almost immediate. Clinicians are familiar with its effects: mute patients can speak again, akinetic patients can move again and patients with negativism can eat and drink again within usually a short duration of about 10 min to 1–2 h. Fear is often gone after lorazepam administration. While not always effective, the introduction of lorazepam into clinical practice represented a breakthrough and was often life-saving for many patients suffering from catatonia. It is rare to observe such rapid therapeutic effects in other domains of psychiatry. In this narrative review we will briefly look at the past, present and future of lorazepam in the treatment of catatonia. It is gratifying to reflect on the fact that clinicians using the age-old medical practice of observation and empirical treatment succeeded in advancing the management of catatonia 40 years ago. The present evidence shows that the clinical effect of lorazepam in catatonia treatment is excellent and more or less immediate although it remains to be explicitly tested against other substances such as diazepam, zolpidem, clozapine, quetiapine, amantadine, memantine, valproate and dantrolene in randomized clinical trials. In addition, future studies need to answer the question how long lorazepam should be given to patients with catatonia, months or even years? This narrative review promotes the rapid use of lorazepam in the treatment of acute catatonic patients and stipulates further scientific examination of its often impressive clinical effects.

GABAergic modulation of performance in response inhibition and interference control tasks.

Inhibitory control is a crucial executive function with high relevance to mental and physical well-being. However, there are still unanswered questions regarding its neural mechanisms, including the role of the major inhibitory neurotransmitter, γ-aminobutyric acid (GABA). This study examined the effects of lorazepam (0.5 mg and 1 mg), a positive allosteric modulator at the GABAA receptor, on response inhibition and interference control. We also explored the heterogeneity of inhibitory control and calculated delta plots to explore whether lorazepam affects the gradual build-up of inhibition and activation over time. N = 50 healthy participants performed antisaccade, Eriksen flanker and Simon tasks in a within-subjects, placebo-controlled, double-blind randomized design. Lorazepam increased reaction time (RT) and error rates dose dependently in all tasks (p ⩽ 0.005). In the antisaccade and Simon tasks, lorazepam increased congruency effects for error rate (p ⩽ 0.029) but not RT (p ⩾ 0.587). In the Eriksen flanker task, both congruency effects were increased by the drug (p ⩽ 0.031). Delta plots did not reflect drug-induced changes in inhibition and activation over time. Delta plots for RT in the Simon task were negative-going, as expected, whereas those for the antisaccade and flanker tasks were positive-going. This study provides evidence for GABAergic involvement in performance on response inhibition and interference control tasks. Furthermore, our findings highlight the diversity of the broader construct of inhibitory control while also pointing out similarities between different inhibitory control tasks. In contrast to RT and error rates, the cognitive processes indexed by delta plots may not be sensitive to GABAergic modulation.

Topiramate as Possible Treatment for Catatonia in Anti-NMDA Receptor Encephalitis

Anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis is a disorder characterized by the presence of pathological auto-antibodies, frequently paraneoplastic, and presenting primarily in young women. The condition has a variable neuropsychiatric presentation, with symptoms frequently including agitation, psychotic symptoms, behavioral changes, generalized or partial seizures, autonomic abnormalities, and hypoventilation. Catatonic symptoms are also frequently present. Catatonia is a syndrome of unclear pathophysiology, hypothesized to be caused by an underlying dysfunction in the GABA­ergic system and typically treated with the benzodiazepine lorazepam or electroconvulsive therapy (ECT). However, there is also evidence for the involvement of glutamate in catatonia, as well as the efficacy of glutamatergic agents, including amantadine, memantine, and topiramate. Here, the authors present the case of a 20-year-old female patient who was admitted with a severe catatonia in the setting of anti-NMDA receptor encephalitis. Because of concerns for side effects of lorazepam and ECT, the patient elected to try a different treatment. Topiramate was chosen due to its good tolerability, prior evidence of efficacy in catatonia (though not in cases of anti-NMDA receptor encephalitis), and its mechanism of action on both GABA receptors and on kainate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors. The patient improved rapidly with the treatment. To the authors' knowledge, this is the first published case of successful treatment of catatonia in anti-NMDA receptor encephalitis with topiramate.

Effects of lorazepam on prosaccades and saccadic adaptation.

Benzodiazepines have reliable adverse effects on saccadic eye movements, but the impact of sex as a potential modulator of these effects is less clear. A recent study reported stronger adverse effects on the spatial consistency of saccades in females, which may reflect sex differences in cerebellar mechanisms. We aimed to further examine the role of sex as a potential modulator of benzodiazepine effects by employing the saccadic adaptation paradigm, which is known to be sensitive to cerebellar functioning. A total of n=50 healthy adults performed a horizontal step prosaccade task and a saccadic adaptation task under 0.5 mg lorazepam, 1 mg lorazepam and placebo in a double-blind, within-subjects design. In the prosaccade task, lorazepam had adverse effects on measures of peak velocity, latency and spatial consistency. The administration of 0.5 mg lorazepam led to significant reductions in gain-decrease adaptation, while a dose of 1 mg did not impair adaptation learning. Gain-increase adaptation was generally less pronounced, and unaffected by the drug. There were no significant drug×sex interactions in either task. We conclude that a low dose of lorazepam impairs gain-decrease adaptation independent of sex. At higher doses, however, increasing fatigue may facilitate adaptation and thus counteract the adverse effects observed at lower doses. With regards to prosaccades, our findings confirm peak velocity as well as latency and spatial measures as sensitive biomarkers of GABAergic effects.

Transcranial Magnetic Stimulation and H1-Magnetic Resonance Spectroscopy Measures of Excitation and Inhibition Following Lorazepam Administration

This study aimed at better understanding the neurochemistry underlying transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS) measurements as it pertains to GABAergic activity following administration of allosteric GABAA receptor agonist lorazepam. Seventeen healthy adults (8 females, 26.0 ± 5.4 years old) participated in a double-blind, crossover, placebo-controlled study, where participants underwent TMS and MRS two hours after drug intake (placebo or lorazepam; 2.5 mg). Neuronavigated TMS measures reflecting cortical inhibition and excitation were obtained in the left primary motor cortex. Sensorimotor cortex and occipital cortex MRS data were acquired using a 3T scanner with a MEGA-PRESS sequence, allowing water-referenced [GABA] and [Glx] (glutamate + glutamine) quantification. Lorazepam administration decreased occipital [GABA], decreased motor cortex excitability and increased GABAA-receptor mediated motor cortex inhibition (short intracortical inhibition (SICI)). Lorazepam intake did not modulate sensorimotor [GABA] and TMS measures of intra-cortical facilitation, long-interval cortical inhibition, cortical silent period, and resting motor threshold. Furthermore, higher sensorimotor [GABA] was associated with higher cortical inhibition (SICI) following lorazepam administration, suggesting that baseline sensorimotor [GABA] may be valuable in predicting pharmacological or neuromodulatory treatment response. Finally, the differential effects of lorazepam on MRS and TMS measures, with respect to GABA, support the idea that TMS measures of cortical inhibition reflect synaptic GABAergic phasic inhibitory activity while MRS reflects extrasynaptic GABA.

Determination of Lorazepam in Drug Formulation and Biofluids Using a Spectrophotometric Method and Response Surface Methodology

A novel, simple, sensitive, and selective kinetic spectrophotometric method has been developed for the determination of lorazepam in pharmaceutical and bioloical samples. The procedure is based on the catalytic effect of lorazepam on the Janus Green–bromate reaction system. The change in absorbance was followed spectrophotometrically at 618 nm. To obtain the maximum sensitivity, the reagents concentration, temperature, and time were optimized by one at the time method. Under optimum experimental conditions, the calibration curve was linear over the range 0.3–19.5 μg/mL of lorazepam, including two linear segments. The relative standard deviations (n = 5) for 1.0, 5.0, and 15.0 μmol/L of lorazepam were 1.09, 1.03, and 0.97%, respectively. The limit of detection was 0.08 μg/mL of lorazepam. An experimental check under these optimal conditions confirmed good agreement in the RSM results. The developed method was successfully applied for the determination of lorazepam in real samples, and the obtained results are in a good agreement with those using HPLC.

Effects of Lorazepam on Ovary and Ovulation of Balb/C adult Female Mouse

Effects of Lorazepam on Ovary and Ovulation of Balb/C adult Female Mouse

Differentiating anxiety from fear: an experimental-pharmacological approach.

Gray's theory of personality postulates that fear and anxiety are distinct emotional systems with only the latter being sensitive to anxiolytic drugs. His work was mainly based on animal research, and translational studies validating his theory are scarce. Previous work in humans showed an influence of the benzodiazepine lorazepam on both systems, however, dependent on dosage (1 and 2 mg) and personality differences in negative emotionality. The present study aims to replicate these findings, and in addition tests the drug threshold effect by introducing a lower dosage of 0.5 mg lorazepam. Fifty healthy adults (23 males, agemean 22.40, SD ± 3.68) participated in an experimental threat-avoidance paradigm designed to dissociate risk assessment intensity (RAI, reflecting anxiety) and flight intensity (FI, reflecting fear) and completed two self-report questionnaires assessing facets of negative emotionality (Spielberger State Trait Anxiety Inventory and Fear Survey Schedule). In a randomized placebo-controlled within-subjects design, 0.5 and 1 mg of lorazepam were applied per os. Saccadic peak velocity was assessed by means of eye-tracking in order to control for sedating drug effects. Results showed the expected and specific anxiolytic effect of lorazepam on RAI, however, only in the 0.5 mg condition. FI was not influenced by lorazepam, and previous findings of interaction effects of lorazepam with self-reported negative emotionality could not be corroborated. Overall, this study demonstrates anxiolytic effects of lorazepam in dosages ≤1 mg in the absence of a drug effect on fear using a translational behavioural task. However, a putative moderating role of personality on defensive behaviour has to be clarified in future research.

Comparison of diazepam and lorazepam for the emergency treatment of adult status epilepticus: a systemic review and meta-analysis.

Status epilepticus (SE) is a life-threatening medical and neurological emergency. Prompt recognition and treatment are essential to stop the seizure and improve patient outcomes. To elucidate which benzodiazepine should be used as the first-line treatment, a systemic search of the PubMed, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases was carried out to identify randomized controlled trials (RCTs) comparing i.v. administration of lorazepam and diazepam used for adult SE. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Only two RCTs were finally analyzed among 2182 papers extracted. The SE definitions, inclusion criteria, and doses of the drugs differed in the two studies. Of 204 patients included, 103 and 101 patients were allocated to the lorazepam and diazepam groups, respectively. The pooled risk ratio (RR) and confidence interval (CI) for lorazepam treatment on seizure cessation (two RCTs, n=204) showed a significantly superior effect of lorazepam over diazepam (RR, 1.24; 95% CI, 1.03-1.49). No statistically significant relationship was found for mortality (two RCTs, n=204) (RR 0.43; 95% CI, 0.43-6.90), poor neurological outcome (one RCT, n=134) (RR, 1.10; 95% CI, 0.59-2.04), hypotension (one RCT, n=70) (RR, 2.68; 95% CI, 0.11-63.61), and respiratory depression (two RCTs, n=204) (RR, 1.07; 95% CI, 0.48-2.48). The certainty of the evidence was rated as very low. The results of this meta-analysis of RCTs showed that i.v. lorazepam was better than i.v. diazepam for the cessation of adult SE.

T175. The Effects of Lorazepam on Resting-State Functional Connectivity

Benzodiazepines, such as lorazepam, are commonly used to treat anxiety. The pharmacological mechanism of action of benzodiazepines is well understood; however, it remains unclear which neural networks and systems are involved during resting-state functional connectivity. The objective of this study is to investigate the effects of lorazepam administration (12 hours or less prior to rsMRI) compared to non-lorazepam during the resting state in patients with psychosis. We focused our analyses on the effects of lorazepam on corticostriatal connectivity, as we have previously demonstrated that a specific pattern of striatal connectivity, the striatal connectivity index (SCI; Sarpal et al., 2016), was related to antipsychotic drug response.

Effects of lorazepam and baclofen on short- and long-latency afferent inhibition.

Short-latency afferent inhibition (SAI) is modulated by GABAA receptor activity, whereas the pharmacological origin of long-latency afferent inhibition remains unknown. This is the first study to report that long-latency afferent inhibition (LAI) is reduced by the GABAA positive allosteric modulator lorazepam, and that both SAI and LAI are not modulated by the GABAB agonist baclofen. These findings advance our understanding of the neural mechanisms underlying afferent inhibition. The afferent volley evoked by peripheral nerve stimulation has an inhibitory influence on transcranial magnetic stimulation induced motor evoked potentials. This phenomenon, known as afferent inhibition, occurs in two phases: short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI). SAI exerts its inhibitory influence via cholinergic and GABAergic activity. The neurotransmitter receptors that mediate LAI remain unclear. The present study aimed to determine whether LAI is contributed by GABAA and/or GABAB receptor activity. In a double-blinded, placebo-controlled study, 2.5mg of lorazepam (GABAA agonist), 20mg of baclofen (GABAB agonist) and placebo were administered to 14 males (mean age 22.7±1.9 years) in three separate sessions. SAI and LAI, evoked by stimulation of the median nerve and recorded from the first dorsal interosseous muscle, were quantified before and at the peak plasma concentration following drug ingestion. Results indicate that lorazepam reduced LAI by ∼40% and, in support of previous work, reduced SAI by ∼19%. However, neither SAI, nor LAI were altered by baclofen. In a follow-up double-blinded, placebo-controlled study, 10 returning participants received placebo or 40mg of baclofen (double the dosage used in Experiment 1). The results obtained indicate that SAI and LAI were unchanged by baclofen. This is the first study to show that LAI is modulated by GABAA receptor activity, similar to SAI, and that afferent inhibition does not appear to be a GABAB mediated process.

Geriatrics Literature 2017 Year in Review.

We present 11 of the most effective articles from 2017 in geriatric medicine. Studies address topics including self-driven advance care planning, unnecessary emergency department transfers from assisted living, effect of transcatheter aortic valve implantation on cognition, a modified Hospital Elder Life Program to reduce delirium after surgery, patient experience and provider understanding of nursing home placement, patient perspectives on recommendations to stop cancer screening, management of subclinical hypothyroidism, reduction of inappropriate medications in nursing homes, effect of lorazepam on end-of-life agitated delirium, and benefits of a novel exercise program on walking.

Impact of adjuvant lorazepam with granisetron on chemotherapy-induced nausea and vomiting in pediatric patients with acute lymphoblastic leukemia.

Chemotherapy-induced nausea and vomiting (CINV) affects quality of life for patients with cancer undergoing chemotherapy. We aimed to assess the effect of lorazepam with granisetron on CINV in children with acute lymphoblastic leukemia (ALL). We reviewed the records of 71 consecutive patients with newly diagnosed ALL who received chemotherapy including vincristine, anthracycline, and systemic steroids between January 2011 and December 2016 in our hospital. The number of chemotherapy cycles reviewed was 164. All patients received granisetron as CINV prophylaxis. Nausea was observed in 51/71 patients (72%) and 93/164 cycles (57%). Vomiting was observed in 47/71 patients (66%) and 79/164 cycles (48%). Age and gender distribution were not significantly different between patients who received lorazepam at the initiation of the chemotherapy cycle (LZP group, n = 30) and those who did not receive lorazepam (non-LZP group, n = 134). There were no significant differences in the incidence of CIN and CIV between the LZP group and non-LZP group (CIN, 67% vs. 57%, P = 0.31; CIV, 53% vs. 47%, P = 0.98). In multivariate logistic regression, female gender and older age (> 5years) were significant risk factors for CIV (female, odds ratio (OR) 2.5, 95% confidence interval (CI) 1.3-5.0, P = 0.007; older age, OR 2.5, CI 1.3-4.8, P = 0.008). We found no beneficial effect of providing lorazepam as adjuvant antiemetic for prevention of CINV in children with ALL.

Is Metabolic Rate Increased in Insomnia Disorder? A Systematic Review.

Background: Insomnia disorder is a highly prevalent health condition, affecting ~10–15% of the adult population worldwide. A central feature of insomnia is hyperarousal characterized as persistent and increased somatic, cognitive and cortical stimulation. Hyperarousal leads to a state of conditioned arousal that disrupts both sleep and daytime function. Research studies have shown increases in body temperature, heart rate, electroencephalographic activity, catecholamines, and oxygen consumption as a measure of metabolic rate. These findings provide evidence of increased physiological activation in insomnia however results are not consistent. The aim of the systematic review was to determine if metabolic rate in patients with insomnia is increased in keeping with the hyperarousal hypothesis.Methods: We searched Pubmed, Web of Science, CINAHL, PsycINFO, EMBASE, and Scopus databases for observational and interventional studies that have measured metabolic rate in insomnia. Study characteristics were extracted and summarized and a risk of bias was performed for each of the studies.Results: Two reviewers screened 963 abstracts with 35 articles of interest for full-text review. Four articles evaluating 75 participants were included in this systematic review. Two studies showed increased oxygen consumption across 24 h in insomnia patients compared with good-sleeping controls. One study which measured oxygen consumption at only a single timepoint showed no difference between insomnia patients and good-sleeping controls. A further study evaluating the effect of lorazepam on oxygen consumption in patients with chronic insomnia showed that lorazepam reduced metabolic rate during the night time only.Conclusions: These findings show that metabolic rate appears to be increased across 24 h in line with the hyperarousal model of insomnia. However, these increases in metabolic rate in insomnia were minor compared to good-sleeping controls and the clinical significance is unclear. Larger, methodologically robust studies are required to confirm these findings and the effect of any increase in metabolic rate on sleep-wake disturbances or pathophysiology.

4. Suppression of hippocampal kindling seizures by lorazepam and levetiracetam

Introduction Benzodiazepine GABA enhancers and levetiracetam are known to be effective in suppression of kindling seizures, but the effects of these antiepileptic drugs on regional after discharges adjacent to the kindling sits are largely unknown. We explored this issue in a mouse model of hippocampal kindling and compared the effects of lorazepam and levetiracetam on hippocampal and piriform after discharges as the piriform cortex is thought to play a critical role in genesis of kindling seizures. Methods C57 black mice received electrode implantations in unilateral hippocampal CA3 and piriform cortical areas and then underwent twice daily hippocampal stimulation for a few weeks. The effects of antiepileptic drugs were tested in fully kindled mice. Lorazepam (1.5 mg/kg) or levetiracetam (100 mg/kg) was applied by an intra-peritoneal injection 15 or 60 min before hippocampal stimulation. The effects observed following similar saline injections were taken as baseline controls. Results Evoked motor seizures and associated piriform after discharges were abolished by lorazepam whereas the durations of corresponding hippocampal afterdischarges were unchanged from baseline controls (n = 6 mice). Evoked motor seizures and corresponding hippocampal and piriform afterdischarges were significantly decreased by levetiracetam, but shortened afterdischarges were more pronounced in the piriform than in the hippocampal area (n = 6 mice). Summary Lorazepam may suppress motor seizures by inhibiting seizure spread from the stimulated hippocampal focus to the piriform cortex and other brain areas, and levetiracetam may inhibit both focal/hippocampal seizures and seizure spread in our model.

Effects of lorazepam on saccadic eye movements: the role of sex, task characteristics and baseline traits.

Saccadic eye movements are controlled by a network of parietal, frontal, striatal, cerebellar and brainstem regions. The saccadic peak velocity is an established biomarker of benzodiazepine effects, with benzodiazepines reliably reducing the peak velocity. In this study, we aimed to replicate the effects of benzodiazepines on peak velocity and we investigated effects on previously less studied measures of saccades. We also explored the roles of sex, task characteristics and the baseline variables age, intelligence and trait anxiety in these effects. Healthy adults ( N = 34) performed a horizontal step prosaccade task under 1 mg lorazepam, 2 mg lorazepam and placebo in a double-blind, within-subjects design. We replicated the dose-dependent reduction in peak velocity with lorazepam and showed that this effect is stronger for saccades to targets at smaller eccentricities. We also demonstrated that this effect is independent of sex and other baseline variables. Lorazepam effects were widespread, however, occurring on mean and variability measures of most saccadic variables. Additionally, there were sex-dependent lorazepam effects on spatial consistency of saccades, indicating more adverse effects in females. We conclude that saccadic peak velocity is a sensitive and robust biomarker of benzodiazepine effects. However, lorazepam has pronounced effects also on other parameters of horizontal saccades. Sex-dependent drug effects on spatial consistency may reflect cerebellar mechanisms, given the role of the cerebellum in saccadic spatial accuracy.