Effects Of Chlordiazepoxide Research Articles

Effect of Chlordiazepoxide or Haloperidol Oral Premedication during Midazolam-Ketamine Anaesthesia on Physiological and Blood Gas Parameters in Adult Male Bonnet Macaques (Macaca radiata)

Capturing wild animals with minimal stress is crucial to reduce morbidity and mortality. Oral premedicants can ease handling and subsequent anaesthetic administration. This study evaluated anaesthetic protocols and physiological changes during vasectomy in 12 adult male Bonnet Macaques. Group I received 10 mg/kg chlordiazepoxide, and Group II received 1 mg/kg haloperidol orally four hours before midazolam-ketamine anaesthesia. Sedation quality, induction, maintenance, and recovery were assessed. Physiological and blood gas changes were monitored at 0, 5, 10, 15, and 20 minutes. Both groups exhibited sedation post-premedication. Induction, maintenance, and anaesthesia depth were similar. Group I had better analgesia, while Group II had superior muscle relaxation. Blood gas analysis indicated mild stress and respiratory acidosis in both groups, with Group II showing more significant hypoxemia and respiratory acidosis. Haloperidol-premedicated animals were easier to handle but exhibited increased stress parameters compared to chlordiazepoxide-premedicated animals. Recovery was better in Group I. Both protocols effectively induced sedation and anaesthesia in Bonnet Macaques.

Chlordiazepoxide reduces anxiety-like behavior in the adolescent mouse elevated plus maze: A pharmacological validation study

This report evaluates the effects of chlordiazepoxide, a benzodiazepine commonly prescribed to manage anxiety-related disorders in adolescent/pediatric populations, on elevated plus maze (EPM) performance in juvenile mice. This approach was taken because chlordiazepoxide produces anxiolytic-like effects in multiple models in adult rodents, however, less is known about the behavioral effects of this benzodiazepine in juveniles. Thus, we administered a single intraperitoneal injection of chlordiazepoxide (0, 5, or 10 mg/kg) to postnatal day 35 male C57BL/6 mice. Thirty minutes later, mice were allowed to explore the EPM for 5-min. We found that chlordiazepoxide-treated mice (5 and 10 mg/kg) spent more time exploring the open arms of the EPM. No differences in velocity (cm/s) or distance traveled (cm) were observed between the groups. These results indicate that chlordiazepoxide induces anxiolytic-related behavior in adolescent male mice.

Indulging Curiosity: Preliminary Evidence of an Anxiolytic-like Effect of Castor Oil and Ricinoleic Acid.

In the process of validating the elevated zero maze, a common test of anxiety-like behavior, in our laboratory, we demonstrated an anxiolytic-like effect of castor oil and its primary component, ricinoleic acid. We tested the effects of vehicle and chlordiazepoxide in male mice in the elevated zero maze following a 30-min pretreatment time. Chlordiazepoxide is a United States Food and Drug Administration-approved drug that was previously shown to exert anxiolytic-like effects in both the elevated zero maze and elevated plus maze. Chlordiazepoxide was administered at doses of 5 or 10 mg/kg. We used 5% polyoxyl 35 castor oil (Kolliphor® EL) and saline as treatment vehicles and found that the effect of chlordiazepoxide on open zone occupancy and open zone entries was blunted when 5% Kolliphor was used as the vehicle. These tests demonstrated that chlordiazepoxide increased open zone occupancy and entries in the elevated zero maze more effectively when saline was used as the treatment vehicle and that Kolliphor dampened the anxiolytic-like effect of chlordiazepoxide when it was used as the treatment vehicle. Notably, 5% Kolliphor alone slightly increased baseline open zone occupancy and entries. Given that Kolliphor is a derivative of castor oil, we next tested the effect of 5% castor oil and 5% ricinoleic acid, which is a major component of castor oil. We found that both castor oil and ricinoleic acid increased open zone occupancy but not entries compared with saline. Altogether, our findings demonstrate that Kolliphor, castor oil, and ricinoleic acid may exert anxiolytic-like effects in male mice in the elevated zero maze. This potential anxiolytic-like effect of castor oil is consistent with its well-established beneficial effects, including anti-inflammatory, antioxidant, antifungal, and pain-relieving properties.

Risk of prolonged sedation with the use of chlordiazepoxide in alcohol withdrawal treatment

Summary The use of chlordiazepoxide in the treatment of alcohol withdrawal symptoms poses a risk of prolonged sedation with the need of weeks lasting antidote treatment, and extended hospitalization due to active metabolites with very long half-lives. We present four case stories to elucidate this issue. One patient received 800 mg chlordiazepoxide and was treated with flumazenil for 42 days. Another patient was treated with 100 mg chlordiazepoxide. 5 days after administration of chlordiazepoxide, concentrations of chlordiazepoxide and its active metabolite demoxepam, were within therapeutic range, the patient was treated with flumazenil for 6 days. He died after palliative care. The great individual variation in the clinical effect of chlordiazepoxide depends on the activity of the CYP P450 system, especially CYP3A4/A5 and CYPS2C19, which can be impaired in cirrhotic and elderly patients.

Comparison of the Effect of Chlordiazepoxide and Transcranial Alternating Current Stimulation on Blood Potassium Loss Due to Preoperative Anxiety

PurposeThis study evaluated and compared the effect of chlordiazepoxide and transcranial alternating current stimulation (tACS) on changes in blood potassium levels caused by preoperative anxiety. DesignThis randomized, double-blind placebo control study was performed on 100 patients undergoing surgery with the American Society of Anesthesiologists physical status (ASA I) who went through surgery for the first time. MethodsPatients were classified into four groups of real or sham tACS, chlordiazepoxide, and placebo. The Amsterdam Preoperative Anxiety information Scale (APAIS) and serum potassium levels were used to collect data. The results were analyzed using the Kolmogorov-Smirnov tests, independent t test, Pearson correlation, and χ2 test. FindingsThere was no baseline difference between the groups. A significant difference was found between real tACS and the chlordiazepoxide group in plasma potassium level (P = .017). ConclusionsThe results showed that real tACS was more effective than chlordiazepoxide in preventing the decrease of plasma potassium level in the preoperative period. Assessing the efficacy of the other types of brain electrical interventions is suggested for future studies.

Further disentangling the motivational processes underlying benzodiazepine hyperphagia

In addition to their well-known anxiolytic functions, benzodiazepines produce hyperphagia. Previously, we reported that the benzodiazepine, chlordiazepoxide (CDP), increased consumption of both normally-preferred and normally-avoided taste stimuli during long-term (1 h) tests, primarily through changes in licking microstructure patterns associated with hedonic taste evaluation, whereas there was little effect on licking microstructure measures associated with post-ingestive feedback. In this study, we further examined the hedonic and motivational specificity of CDP effects on ingestive behavior. We tested brief access (15 s) licking responses for tastants spanning all taste qualities after treatment with either CDP (5 or 10 mg/kg) or the non-benzodiazepine anxiolytic, buspirone (1.5 or 3 mg/kg). A between-subjects, counterbalanced design compared the CDP or buspirone effects on licking responses for water and a range of weak to strong concentrations of NaCl, Q-HCl, citric acid, MSG, saccharin, and capsaicin under water-restricted (23 h) conditions; and sucrose, saccharin, and MSG under water-replete conditions. In a dose dependent manner, CDP increased licking for taste stimuli that were normally-avoided after saline treatment, with a notable exception observed for the trigeminal stimulus, capsaicin, which was not affected at any concentration or drug dose, suggesting a taste-specific effect of CDP on orosensory processing. Under water-replete conditions, CDP dose-dependently increased licking to normally-accepted concentrations of sucrose, saccharin, and MSG. There was no effect of either drug on licks for water under either water-restricted or water-replete conditions. Buspirone slowed oromotor coordination by increasing brief interlick intervals, but it did not affect licking for any concentrations of the tastants. Overall, these results indicate that benzodiazepines selectively enhance the hedonic acceptance of gustatory orosensory stimuli, independent of general anxiolytic or oromotor coordination effects, or physiological states such as thirst.

Effects of chlordiazepoxide on pausing during rich-to-lean transitions.

Extended pausing during discriminable transitions from rich-to-lean conditions can be viewed as escape (i.e., rich-to-lean transitions function aversively). Thus, an anxiolytic drug would be predicted to mitigate the aversiveness and decrease pausing. In the current experiment, pigeons' key pecking was maintained by a multiple fixed-ratio fixed-ratio schedule of rich (i.e., larger) or lean (i.e., smaller) reinforcers. Intermediate doses (3.0-10.0 mg/kg) of chlordiazepoxide differentially decreased median pauses during rich-to-lean transitions. Relatively small decreases in pauses occurred during lean-to-lean and rich-to-rich transitions. Effects of chlordiazepoxide on pausing occurred without appreciable effects on run rates. These findings suggest that signaled rich-to-lean transitions function aversively.

Effects of linalool on extinction of mouse operant behaviour.

Linalool is an enanitomer monoterpene compound identified as the pharmacologically active constituent in a number of essential oils and has been reported to display anxiolytic properties in humans and in animal models and to exert both GABAergic and glutamatergic effects. In Experiment 1 linalool (100, 200, and 300, i.p.) had no significant effects compared with saline in an activity tracker with C57BL/6j mice. Experiment 2 assessed the effects on operant extinction with mice of chlordiazepoxide at a dose (15 mg/kg, i.p.) previously shown to facilitate extinction, and the same doses of linalool, compared with saline. Linalool had a dose-related facilitatory effect on extinction. While the effects of the highest dose of linalool most closely resembled the effects of chlordiazepoxide, the pattern of results suggested that linalool may affect both the acquisition of extinction learning, which is influenced by glutamatergic processes, and the expression of extinction, known to be affected by GABAergic agents such as chlordiazepoxide.

P.421 Effect of chlordiazepoxide on a rat model of ultrasound-induced panic attack

P.421 Effect of chlordiazepoxide on a rat model of ultrasound-induced panic attack

Establishing operant conflict tests for the translational study of anxiety in mice

In conflict-based anxiety tests, rodents decide between actions with simultaneous rewarding and aversive outcomes. In humans, computerised operant conflict tests have identified response choice, latency, and vigour as distinct behavioural components. Animal operant conflict tests for measurement of these components would facilitate translational study. In C57BL/6 mice, two operant conflict tests for measurement of response choice, latency, and vigour were established, and effects of chlordiazepoxide (CDZ) thereon investigated. Mice were moderately diet-restricted to increase sucrose reward salience. A 1-lever test required responding under medium-effort reward/threat conditions of variable ratio 2-10 resulting in sucrose at p= 0.7 and footshock at p= 0.3. A 2-lever test mandated a choice between low-effort reward/threat with a fixed-ratio (FR) 2 lever yielding sucrose at p= 0.7 and footshock at p= 0.3 versus high-effort reward/no threat with a FR 20 lever yielding sucrose at p= 1. In the 1-lever test, CDZ (7.5 or 15mg/kgi.p.) reduced post-trial pause (response latency) following either sucrose or footshock and reduced inter-response interval (increased response vigour) after footshock. In the 2-lever test, mice favoured the FR2 lever and particularly at post-reward trials. CDZ increased choice of FR2 and FR20 responding after footshock, reduced response latency overall, and increased response vigour at the FR2 lever and after footshock specifically. Mouse operant conflict tests, especially 2-lever choice, allow for the translational study of distinct anxiety components. CDZ influences each component by ameliorating the impact of both previous punishment and potential future punishment.

The contribution of contextual fear in the anxiolytic effect of chlordiazepoxide in the fear-potentiated startle test

This study evaluated the extent to which a reduction in contextual fear contributes to the anxiolytic effect of benzodiazepines in the fear-potentiated startle response. To this end, chlordiazepoxide, an anxiolytic often used as positive control in preclinical drug studies, and zolpidem, known to have sedative properties and to be devoid of anxiolytic effects, were tested in two contexts: the same context as training had taken place and an alternative context. In addition, the level of muscle relaxation was assessed in a grip strength test. Chlordiazepoxide (2.5–10 mg/kg) decreased the fear-potentiated startle response, confirming its anxiolytic activity. In addition, it dose-dependently decreased the overall startle response in the same, but not the alternative context, and did not affect grip strength, indicating that chlordiazepoxide inhibits contextual fear in the absence of non-specific drug effects. Zolpidem (1.0–10 mg/kg) reduced the overall startle response in both contexts equally and decreased grip strength, indicating that its effects on fear-potentiated startle are due to non-specific drug effects, and not anxiolytic effects. The present findings show that chlordiazepoxide reduces contextual conditioned fear in the absence of non-specific drug effects. In addition, they show that training and testing rats in different contexts makes it possible to distinguish between cued, contextual and non-specific drug effects. As exaggerated contextual fear conditioning contributes to the fear generalization processes implicated in pathological anxiety, focus in screening of anxiolytic effects could be directed more towards the suppression of contextual fear and, therefore, this approach would be a valuable addition to standard preclinical screening.

Proximity as a predictor of social behavior in rats

BackgroundIn studies that measure social behavior of a freely interacting pair rats social behavior of one rat is strongly influenced by the behavior of the other. This prevents evaluating social behavior of one single rat. New methodWe assessed the motivation to interact socially in a modified open-field, by measuring the time a rat attempted to interact with a co-specific separated by a grid in a birdcage outside of the apparatus. We propose time in front of the birdcage is an indicator of social behavior. ResultsWe showed that the focal rat allocates more time in front of the birdcage, interacting with another rat through the grid. Also, that the presence of the other rat that attracts the focal rat. Habituation to the apparatus, repeated testing and illumination condition did not alter the proximity measures of rats. Finally, treatment with chlordiazepoxide (3.0mg/kg) either increased the time spent in front of the cage by males and females or (5.6mg/kg) increased the proximity measure of females. Comparing with existing methodOur method prevents partners from influencing the target rat’s social behavior; existing methods do not. Also, it is more sensitive to the effect of chlordiazepoxide than the broadly used method proposed by File and Hyde (1978). ConclusionsProximity is an advantageous measure: it allows the assessment of only one focal animal without the interference of a partner; it is simple to take; it requires little interpretation skills or training from the experimenter, no special equipment or conditions.

Assessing anxiety in C57BL/6J mice: A pharmacological characterization of the open-field and light/dark tests

Introduction: In order to assess anxiety in mammals various tests and species are currently available. These current assays measure changes in anxiety-like behaviors. The open-field and the light/dark are anxiety tests based on the spontaneous behavior of the animals, with C57BL/6J mice being a frequently used strain in behavioral studies. However, the suitability of this strain as a choice in anxiety studies has been questioned. In this study, we performed two pharmacological characterizations of this strain in both the open-field and the light/dark tests. Methods: We examined the changes in the anxiety-like behaviors of C57BL/6J mice exposed to chlordiazepoxide (CDP), an anxiolytic drug, at doses of 5 and 10mg/kg, picrotoxine (PTX), an anxiogenic drug, at doses of 0.5 and 1mg/kg, and methylphenidate (MPH), a psychomotor stimulant drug, at doses of 5 and 10mg/kg, in a first experiment. In a second experiment, we tested CDP at 2.5mg/kg, PTX at 2mg/kg and MPH at 2.5mg/kg. Results: Results showed an absence of anxiolytic-like effects of CDP in open-field and light/dark tests. Light/dark test was more sensitive to the anxiogenic effects of PTX than the open-field test. Finally, a clear anxiogenic effect of MPH was observed in the two tests. Discussion: Although C57BL/6J mice could not be a sensitive model to study anxiolytic effects in pharmacological or behavioral interventions, it might be a suitable model to test anxiogenic effects. Further studies are necessary to corroborate these results.

Memory interfering effects of chlordiazepoxide on consummatory successive negative contrast

Long–Evans rats downshifted from 32% to 4% sucrose solution exhibit lower consummatory behavior during downshift trials than rats exposed only to 4% sucrose. In Experiment 1, this effect, called consummatory successive negative contrast (cSNC), was attenuated by administration of the benzodiazepine anxiolytic chlordiazepoxide (CDP, 5mg/kg, ip) before the second downshift trial (Trial 12), but was not affected when CDP was administered before the first downshift trial (Trial 11). In Experiment 2, CDP administered after Trial 11 actually enhanced the cSNC effect on Trial 12. This posttrial effect of CDP was reduced by delayed administration (Experiment 3). This CDP effect was not present in the absence of incentive downshift (Experiments 4–5), or when animals were tested with the preshift incentive (Experiment 6) or after complete recovery from cSNC (Experiment 7). The posttrial CDP effect was observed after an 8-day interval between Trials 11 and 12 (Experiment 8) and when administered after Trial 12, rather than Trial 11 (Experiment 9). Experiment 10 extended the effect to Wistar rats. Because CDP is a memory interfering drug, it was hypothesized that its posttrial administration interferes with the consolidation of the memory of the downshifted incentive, thus prolonging the mismatch between expected (32% sucrose) and obtained (4% sucrose) incentives that leads to the cSNC effect.

The effects of chlordiazepoxide andd-amphetamine during a three-component multiple schedule

Multiple schedules have been used in behavioral pharmacology research to show that a drug's effect on behavior can be a function of the schedule of reinforcement that supports that behavior. However, less research has examined whether the context of the schedule of reinforcement in a multiple schedule can change the drug's effect on behavior. We examined the effects of acute chlordiazepoxide and d-amphetamine injections on the behavior of two groups of pigeons trained on a three-component multiple schedule with identical schedules of reinforcement in the first and last components. For one group of pigeons reinforcement was unavailable during the middle component (decreased-middle-component). For the second group reinforcement rate was higher during the middle component than during the first or third components (increased-middle-component). In the decreased-middle-component group, chlordiazepoxide (3.2-32 mg/kg) decreased third-component response rates less than it decreased responding in the first component. Conversely, in the increased-middle-component group, chlordiazepoxide (3.2-10 mg/kg) decreased third-component response rates more than in the first component. In both groups, d-amphetamine did not differentially affect response rates across components. These results are consistent with previous research showing that drugs can differentially affect responding to two different schedules of reinforcement during the same session, and suggest that pharmacological preparations may be helpful in elucidating the mechanisms that control multiple schedule interactions.

Neurophysiological and behavioural effects of lavender oil in rats with experimentally induced anxiety

This study examined anxiolytic effects of lavender oil on brain serotonin levels and anxiety-related behaviours of rats. The experimental rats were divided into five groups, which respectively received inhalation of saline, 1.25% lavender oil, 2.5% lavender oil, chlordiazepoxide (CDP), and 2.5% lavender oil co-administered with CDP. Anxiety was induced in rats using animal models including Elevated Plus Maze and Open Field. The levels of serotonin in the pre-frontal cortex and striatum of the rats, the anxiolytic effects of lavender oil and its augmentation effect as to co-administration with CDP were evaluated. The neurophysiological findings showed that groups receiving lavender oils, CDP, and 2.5% lavender oils co-administered with CDP had significantly higher level of serotonin in the pre-frontal cortex. However, the anxiolytic behavioural effects of lavender oil were found to have mixed results. This study provided preliminary evidence that inhalation of lavender oil paralleled effects of CDP in up-regulating synthesis of serotonin in rat pre-frontal cortex, and the co-administration of CDP with 2.5% lavender oil tended to augment effect of CDP on serotonin in their pre-frontal cortex and striatum. Copyright © 2013 John Wiley & Sons, Ltd.

Role of gamma-aminobutyric acid type A (GABAA) receptor subtypes in acute benzodiazepine physical dependence-like effects: evidence from squirrel monkeys responding under a schedule of food presentation

Assays of schedule-controlled responding can be used to characterize the pharmacology of benzodiazepines and other GABAA receptor modulators, and are sensitive to changes in drug effects that are related to physical dependence. The present study used this approach to investigate the role of GABAA receptor subtypes in mediating dependence-like effects following benzodiazepine administration. Squirrel monkeys (n = 6) were trained on a fixed-ratio schedule of food reinforcement. Initially, the response rate-decreasing effects of chlordiazepoxide (0.1-10mg/kg; nonselective GABAA receptor agonist), zolpidem (0.032-1.0mg/kg; α1 subunit-containing GABAA subtype-preferring agonist), and HZ-166 (0.1-10mg/kg; functionally selective α2 and α3 subunit-containing GABAA receptor agonist) were assessed. Next, acute dependence-like effects following single injections of chlordiazepoxide, zolpidem, and HZ-166 were assessed with flumazenil (0.1-3.2mg/kg; nonselective GABAA receptor antagonist). Finally, acute dependence-like effects following zolpidem administration were assessed with βCCt and 3-PBC (0.1-3.2mg/kg and 0.32-10mg/kg, respectively; α1 subunit-containing GABAA receptor antagonists). Chlordiazepoxide, zolpidem, and HZ-166 produced dose- and time-dependent decreases in response rates, whereas flumazenil, βCCT, and 3-PBC were ineffective. After the drug effects waned, flumazenil produced dose-dependent decreases in response rates following administration of 10mg/kg chlordiazepoxide and 1.0mg/kg zolpidem, but not following any dose of HZ-166. Further, both βCCT and 3-PBC produced dose-dependent decreases in response rates when administered after 1.0mg/kg zolpidem. These data raise the possibility that α1 subunit-containing GABAA receptors play a major role in physical dependence-related behaviors following a single injection of a benzodiazepine.

Samuel C Kaim

Samuel C Kaim had a long life. He was born in New York City on 24 November 1911 and died on 24 March 2012 in Washington, DC. During this period, he saw and contributed to the birth and enormous growth of our field. His undergraduate training was in Cleveland at Western Reserve (Case Western) and his medical training in Switzerland at the University of Zurich, with a residency there at the Burgholzli Clinic. For his first, direct exposure to psychopharmacology, he was charged with administering insulin and metrazole seizure therapies. With little doubt, the residency had many influences on his later career. He conducted a private practice for several years in Illinois, interrupted by 4 years as a medical officer during WWII. In 1950, he took what was to be the first of many positions in the VA. First, he headed psychiatry and neurology at the VA Hospital in Coral Gables, Florida. The VA was becoming a major source of clinical trials at the time and Sam participated in these, using EEG techniques, and was among the first to show the profound effects of chlordiazepoxide in reducing or preventing both seizures and delirium tremens in alcohol withdrawal. In 1960, he went to the central office of the VA to become the head of research nationwide for psychiatry and neurology. He became a strong advocate of VA Cooperative Studies and decided to use this mechanism to pursue the benefits of chlordiazepoxide in the alcohol withdrawal syndrome, and it became widely recognized as the drug of choice for this use. The VA had been slow to recognize alcoholism as worthy of its own service. After considerable advocacy, Sam became the first director of an Alcoholism Service in the VA. He helped to compel armed forces personnel to recognize the significance of opioid dependence in Vietnam, leading a charge for expansion of his office in 1970 to become the Alcohol and Drug Dependence Services. Through his VA appointment, Sam had the opportunity to work with Jerome Jaffe when Jerry headed the Special Action Office for Drug Abuse Prevention. Together with their colleagues, they focused on development of the long-acting methadone, ℒ-α-acetyl-methadol (LAAM) for heroin treatment, and on development of naltrexone, the long-acting narcotic antagonist, as a useful agent in heroin addiction. Though it took until 1993 for LAAM to be approved by the FDA, their perseverance had an important role in the survival of these interesting interventions. Certainly, we have yet to discover the final place of naltrexone in medicine. Sam left the VA in 1975 and became director of staff of the National Academy of Sciences that coordinated one of the pilot studies of naltrexone in the treatment of heroin abuse. He was also a consultant to NIDA in a variety of roles through to the approval of naltrexone for marketing by the FDA. He vigorously continued a variety of activities with professional organizations until he retired in 1993. Those of you who enjoy good collegial conversation will be delighted by the interview conducted by Leo Hollister of the then 85-year-old Sam for our History of the ACNP. It illustrates many, many of the interesting characteristics of Sam. Sam Kaim is survived by his son, Edward, of Weston, Connecticut, and two stepchildren, Judith Plavnick Kiley of Arlington, Virginia, and Jonathan Plavnick of Perry Hall, Maryland.

Working memory in the odor span task: effects of chlordiazepoxide, dizocilpine (MK801), morphine, and scopolamine

A number of tasks are used to assess working memory in rodents, but the odor span task (OST) is unique in studying performance as a function of the number of stimuli to remember. The purpose of the present study was to better characterize the behavioral pharmacology of the OST by exploring the effects of several amnestic agents including an NMDA antagonist (dizocilpine), a positive GABA-A modulator (chlordiazepoxide), an anticholinergic compound (scopolamine), and as a negative control, an opiate receptor agonist (morphine). Rats were trained to perform on the OST which is a non-match-to-sample procedure with an incrementing number of sample odors to remember as the session progresses. Trials with a simple odor discrimination task (SD) were interspersed to provide a control for effects unrelated to memory load. All four drugs disrupted performances on the OST task in a dose-dependent fashion, but only the NMDA antagonist dizocilpine produced impairments that were clearly dependent on the number of stimuli to remember. Dizocilpine impaired OST performance at a dose (0.1 mg/kg) that did not affect SD, and that impairment depended on memory load. Chlordiazepoxide (3.0 mg/kg) also produced amnestic effects that were manifest by shorter memory spans and runs of correct responding. In contrast, morphine and scopolamine impaired OST accuracy only at doses that also disrupted SD (18.0 and 0.3 mg/kg, respectively). These results provide evidence of NMDA and benzodiazepine modulation of working memory as assessed by the OST.

The effect of chlordiazepoxide on measures of activity and anxiety in Swiss-Webster mice in the triple test

The effects of the anxiolytic drug chlordiazepoxide (CDZ) on general activity and anxiety-related behaviour of male and female Swiss-Webster mice were investigated in the triple test, which combines the open field (OF), elevated-plus maze (EPM) and the light–dark box (LDB). Mice were injected with saline or CDZ (1.0, 7.5 or 15.0 mg/kg) and their behaviour was observed for 15 min in the triple test on each of two days. On day 1, increasing doses of CDZ increased open arm exploration and total distance travelled, and decreased risk assessments in the EPM. In the LDB, CDZ increased time in the light compartment and number of transitions between compartments. In spite of habituation to the apparatus, CDZ increased the number of transitions in the LDB, increased percent time in the open arms and total distance travelled in the EPM on day 2. Thus, there was a significant effect of CDZ in the triple test on both days, even though there was habituation to the apparatus after day 1. These results show that the drug effect was independent of the day effect and that there was no one-trial tolerance effect in the triple test of anxiety.