Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DIAZEPAM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMed1982

Diazepam reverses bombesin-induced gastric spasms and food intake reduction in the rat.

Bombesin (2-16 micrograms/kg, i.p.) produced abnormally large gastric contractions in intact rats consisting of increases in gastric pressure and motility. The effect was antagonized by diazepam (5 mg/kg, i.p.). The same dosage of diazepam abolished bombesin-induced food intake reduction. Diazepam by itself did not increase food intake above control levels. The time course of this behavioral antagonism was followed. There was no significant difference in the intake time course of diazepam-alone and diazepam-bombesin treatments, while there was a significant difference between the saline control and the bombesin-alone treatments. Intake of the saline control, the diazepam-alone and the diazepam-bombesin treatment terminated at the same level, while the bombesin-alone remained significantly different. Additionally, swift aversion to 8 micrograms/kg bombesin was obtained when flavored nutrient was substituted for flavored water, suggesting that the aversion developed as a consequence of interaction with the ingested diet. Abnormalities that result from intake reduction is due to the bombesin-produced intragastric abnormalities, and not by satiety.

Animals↗
PubMed1989

Atropine and/or diazepam therapy protects against soman-induced neural and cardiac pathology.

Toxic doses of the organophosphonate anticholinesterase agent soman can produce neural and cardiac lesions in animals that survive the acute poisoning. The ability of two standard antidote drugs, atropine and diazepam, along with the oxime pralidoxime (2-PAM) Cl, were evaluated for their ability to block these pathological effects. Rats were challenged with a fixed dose (85 micrograms/kg, sc) of soman and treated im 5 min later with 25 mg/kg 2-PAM Cl and one of the following combinations of atropine (0.0, 1.0, 3.2, 10.0, or 32.0 mg/kg) and diazepam (0.0, 0.1, 0.32, 1.0, or 3.2 mg/kg) in a balanced design. The severity of acute anticholinesterase intoxication signs was rated 1 hr after exposure; Body weights and behavioral reactivity ratings were obtained daily for 16 days after exposure; brains and hearts of all surviving subjects were then evaluated for pathological changes. Soman challenge resulted in 33% lethality in animals that received only 2-PAM therapy; both atropine and diazepam reduced lethality in a dose-dependent fashion. Across all treatment conditions greater than 50% of the deaths occurred later than 24 hr after intoxication and treatment. Acute intoxication signs were differentially moderated by the two drugs: atropine reduced all six signs in a dose-dependent fashion; diazepam had no effect on lacrimation and eye bulb protrusion, antagonized signs of salivation and motor abnormalities in a dose-dependent manner, and antagonized the effects of soman on signs of physical activity and coordination only at low doses. All doses of diazepam and the highest dose of atropine moderated body weight loss and a syndrome of behavioral hyperreactivity observed after exposure. Brain pathology was significantly reduced by all doses of diazepam and/or the highest dose of atropine, but no single drug or drug combination was effective in protecting all animals in a group from some brain pathology. Both drugs blocked the development of cardiac lesions in a dose-dependent fashion. The results demonstrate that diazepam or high doses of atropine can antagonize the development of brain lesions that result from soman exposure. Pharmacological management of epileptiform motor abnormalities during the acute intoxication is critical for this effect. In contrast, soman-induced cardiac pathology may occur secondarily as a consequence of the severe brain lesions or develop independently of brain lesion formation due possibly to sympathetic overstimulation.

Animals↗
PubMed1985

Diazepam-ethanol interaction: initial treatment and combined treatment effects.

Water-deprived female Sprague-Dawley rats were trained in a conditioned suppression of drinking paradigm. Experiment 1 assessed the effects of prior experience with ethanol on the initial treatment deficit of diazepam (1A) and the influence of prior experience with diazepam on the initial treatment effects of ethanol (1B). In Experiment 1A, half the animals received three daily doses of ethanol, while the other half received vehicle for 3 days. All rats then received vehicle followed by 3 days of ethanol treatment. No significant effect of prior experience with ethanol was observed on the diazepam initial treatment deficit. In Experiment 1B, half the animals received vehicle followed by three daily doses of diazepam, while the other half received vehicle. All subjects then received vehicle followed by 3 days of ethanol treatment. No significant effect of prior experience with diazepam was noted on ethanol's initial treatment effects. Experiment 2 assessed the effects of diazepam (0, 1, 2, and 4 mg/kg) and ethanol (0, 0.5, 1 and 2 g/kg) alone and in combination in the conflict test. Diazepam, administered alone, resulted in an antipunishment effect. Ethanol alone did not produce an antipunishment effect. The combination of the two drugs generally decreased both punished and unpunished responding. Further, the CNS depressant effects of these drugs appear to be additive. The qualitative effects of these two drugs are different enough to disallow generalization to each other in a conflict test.

Animals↗
PubMed1993

Effects of serotonergic anxiolytics on physical dependence on diazepam in mice.

The effects of serotonergic anxiolytics on the development of physical dependence on diazepam were examined in mice. Co-administration of buspirone (5-HT1A agonist) or ondansetron (5-HT3 antagonist), but not mianserin (5-HT1C antagonist) or ketanserin (5-HT2 antagonist) with diazepam potentiated the hypersensitivity to FG 7142 following chronic treatment with diazepam. This potentiation was not ascribable to pharmacokinetic interactions between diazepam and buspirone or ondansetron. These results suggest that co-administration of buspirone or ondansetron with diazepam may potentiate the development of physical dependence on diazepam; 5-HT1A and 5-HT3 receptors may be partially involved in the development of physical dependence on diazepam.

Animals↗
PubMed1991

Determination of diazepam and nordazepam in milk and plasma in the presence of oxazepam and temazepam.

For studies on the excretion of drugs into milk a sensitive high-performance liquid chromatographic assay was developed to quantitate diazepam and nordazepam in the milk and plasma of humans and rabbits in the presence of their major metabolites, oxazepam and temazepam. Flurazepam was used as an internal standard. The assay involves extractions with diethyl ether and an additional acid clean-up step. Chromatographic separation was achieved by a LiChrospher 60 RP-select B (5 microns) column and KH2PO4- acetonitrile (69:31, v/v) adjusted to pH 2.80 as a mobile phase. The same extraction and chromatographic conditions were suited to both types of samples, milk and plasma. The limits of determination using ultraviolet detection at 241 nm was for diazepam 20 ng/ml and for nordazepam 15 ng/ml. The absolute recoveries of diazepam, nordazepam and flurazepam in human milk were 84, 86 and 92% and in human plasma 97, 89 and 94%, respectively. The within- and between-day accuracy and precision for diazepam and nordazepam in milk and plasma at all concentrations tested (20-1500 ng/ml) were better than 8%. The high fat content which occurs in rabbit milk presented no limitation for the extraction of lipophilic diazepam: the method was successfully used to monitor milk and plasma concentrations of diazepam and nordazepam in lactating New Zealand White rabbits during 26-h infusions of diazepam (1.4 mg/h).

Chromatography, High Pressure Liquid↗
PubMed1995

Characterization of novel ligands for wild-type and natural mutant diazepam-insensitive benzodiazepine receptors.

A series of benzodiazepine receptor ligands with different chemical structures were evaluated for their affinities at diazepam-sensitive and diazepam-insensitive binding sites for [3H]Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-[1,5a][1,4] benzodiazepine-3-carboxylate) in cerebellar GABAA receptors. Rats of Wistar strain and of alcohol-sensitive (ANT) and alcohol-insensitive (AT) lines were used. The ANT rats possess a single point mutation in their GABAA receptor alpha 6 subunit, which makes their diazepam-insensitive sites sensitive to benzodiazepine agonists, unlike those of AT and Wistar rats. All compounds evaluated displayed high-affinity binding to diazepam-sensitive sites (Ki < 50 nM). In contrast, a wider range of affinities were observed at diazepam-insensitive sites which depended upon the basic structure and substitutions. The 7- and 8-halogen substituted imidazobenzodiazepines and 12-halogen substituted diimidazoquinazolines displayed the highest affinities (Ki < 15 nM), while intermediate to low affinities (100 < Ki < 4000 nM) were displayed by imidazoquinazolines, thienopyrimidines, one oxoimidazoquinoxaline, and some cyclopyrrolones. The imidazoquinoxalines evaluated displayed the lowest affinity (Ki > 10000 nM). The oxoimidazoquinoxaline, 6-chloro-3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-4,5-dihydro-5-isop ropyl-4-oxo-imidazo[1,5-a]quinoxaline (NNC 14-0578) and suriclone represent the first benzodiazepine receptor full agonists to bind with relatively high affinity (Ki approximately 100 nM) to diazepam-insensitive sites. The 5 position substituted methoxybenzyl, dimethylallyl, and 4-fluorobenzyl oxoimidazoquinoxaline analogs demonstrated a 58-336-fold higher affinity for ANT than AT diazepam-insensitive sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Postmortem changes in tissue concentrations of triazolam and diazepam in rats.

The aim of this study was to investigate the postmortem changes of concentrations of triazolam and diazepam in the rat model and to confirm the factor causing the phenomenon. We administered triazolam or diazepam orally to rats and then sacrificed them 1 h after administration. Abdominal tissues including stomach content and small intestine, thigh muscle and heart blood were collected at 0, 12, 24 h after death, and postmortem changes of the two drug concentrations were compared. Drug concentrations in the samples were analyzed by a selected ion monitoring of gas chromatography/mass spectrometry. Gastrointestinal postmortem concentrations of triazolam and diazepam decreased. On the other hand, the drug concentrations in the liver and kidney increased markedly, and those in lung and heart blood increased slightly during postmortem periods by diffusion from the gastrointestinal tract. The patterns of both drug concentration changes were similar. However, the extent of the triazolam increase tended to be larger than that of diazepam. This difference may be accounted for by lower triazolam concentrations before death. The postmortem drug concentrations of thigh muscle did not change when administered with triazolam and diazepam. For both triazolam and diazepam, a significant correlation was observed in the drug concentration between the small intestine and the kidney at 24 h after death, indicating that major cause of the change in the drug concentration in the kidney was diffusion from the small intestine up to 24 h after death. The results in this study indicate that diazepam as well as triazolam diffuses from the gastrointestinal tract into the surrounding tissues after death and suggest that the diffusion is influenced by their pharmaceutical properties before death.

Animals↗
PubMed2005

Diazepam effects on Ehrlich tumor growth and macrophage activity in mice.

Besides the central gabaergic receptors described for benzodiazepines, peripheral type binding sites (PBR) were also identified for these molecules in endocrine steroidogenic tissues, immune organs and cells, such as macrophages and lymphocytes. PBR activation was reported to decrease innate immunity and host defense. The present experiment was designed to analyze the effects of diazepam on Ehrlich tumor growth, and on macrophage activity of Ehrlich tumor bearing mice. Results showed that diazepam (3.0 mg/kg/day, for 7 days) increased the number of Ehrlich tumor cells and the volume of tumor-induced ascitic fluid. These effects were not observed after smaller doses of diazepam, suggesting a dose-dependant effect. Furthermore, our results show that 3.0 mg/kg of diazepam, administered daily, for 2 days, decreased (1) the number of peritoneal leukocytes retrieved after injection of the Ehrlich tumor, (2) the percents of macrophage spreading, and (3) the levels of macrophage NO production. Diazepam (3.0 mg/kg/day for 2 days) had no effect on macrophage phagocytosis or on H2O2 production. The present data is discussed based on a direct and/or indirect action of diazepam. Particularly, our findings might be due to a direct effect of diazepam on PBRs present on macrophages and tumor cells, or could still be mediated by PBR stimulation within the hypothalamus-pituitary-adrenal (HPA) axis.

Animals↗
PubMed2005

Diazepam and propofol used as anesthetics during open-heart surgery do not cause chromosomal aberrations in peripheral blood lymphocytes.

Diazepam is a benzodiazepine with anticonvulsant, anxiolytic, sedative and muscle-relaxing properties. Many aspects of its toxicity have been investigated, including genotoxic and carcinogenic effects in various model systems. However, it is still unclear whether diazepam is in fact a genotoxic agent. Propofol is a rapid-onset, short-acting intravenous anesthetic agent. It is used widely for the induction and maintenance of anesthesia as well as for long-term sedation in intensive care units. There is limited information in the literature on its genotoxic effects. Both drugs are commonly used as anesthetic in patients undergoing open-heart surgery. Therefore, we investigated the possible genotoxic effects of propofol and diazepam in those patients, using a chromosomal aberration (CA) assay. Peripheral blood samples were collected from 45 patients before induction of anesthesia and at the end of the anesthesia with diazepam or propofol. In Group I (n=24), anesthesia was induced with 0.2 mg kg(-1) diazepam and 10 microg kg(-1) fentanyl. In Group II (n=21), anesthesia was induced with 1 mg kg(-1) propofol and 10 microg kg(-1) fentanyl. Pancuronium bromide (0.1 mg kg(-1)) was administered for skeletal muscle relaxation in both groups. Anesthesia was maintained by diazepam administration at 5 mg kg(-1) in Group I or by continuous propofol administration at 2-4 mg (kg h)(-1) in Group II. All patients received 0.02 mg kg(-1) pancuronium and 5 microg kg(-1) fentanyl boluses at 30-40 min intervals for anesthesia maintenance. Body temperature was controlled during bypass in the two groups. We found that the mean frequency of CAs in both groups before and at the end of the anesthesia were not statistically significantly different. Our analysis also indicated that age, smoking habit and gender were not confounding factors. In conclusion, our results indicate that diazepam and propofol do not exert genotoxic effects in blood cells during open-heart surgery.

Adult↗
PubMed2006

Reproductive experience reduces the sedative, but not anxiolytic effects of diazepam.

Benzodiazepines are frequently prescribed to women for both their anxiolytic and hypnotic effects. Previous studies in rodents have demonstrated reproductive experience, i.e. pregnancy and lactation, can alter sensitivity to certain drugs, such as morphine. The purpose of the present study was to determine whether reproductive experience alters sensitivity to the benzodiazepine, diazepam. Two groups of subjects were generated, a primparous group (pregnancy+21 days of lactation) and an age-matched, nulliparous group. All subjects were injected with diazepam (0.0, 0.5, 2.0 or 2.5 mg/kg) at least 6 weeks after primiparous females weaned their litters. Twenty minutes post-injection, subjects were place in an activity chamber and locomotor behavior was measured. Thirty minutes post-injection, subjects were tested on an automated elevated plus maze. In addition to behavioral testing, diazepam's effects on corticosterone levels were measured. Overall, diazepam's sedative effects on locomotor activity were significantly reduced in primiparous females when compared to nulliparous controls as determined both in the activity chamber and on the elevated plus maze. There was, however, no significant effect of reproductive experience on the anxiolytic effects of diazepam in the elevated plus maze. Finally, while diazepam increased corticosterone in both groups, primiparous females were less sensitive to the effects of the drug on corticosterone secretion. These results indicate that the effects of diazepam on locomotor activity and corticosterone secretion are attenuated following reproductive experience.

Animals↗
PubMed2000

Differential expression of EGR-1 mRNA in the amygdala following diazepam in contextual fear conditioning.

The amygdaloid complex is thought to be a major site of action of anxiolytic benzodiazepine agonists. To investigate whether activity in the amygdaloid complex is altered with anxiolytic effects of diazepam, mRNA expression of the immediate-early gene EGR-1 was examined in the amygdala following blockade of fear conditioning by diazepam. It was previously shown that mRNA expression of EGR-1 (also called, NGFI-A, Zif 268, Krox 24) increases in the lateral nucleus of the amygdala (LA) shortly following contextual fear conditioning. It was therefore hypothesized that diazepam would block both contextual fear and the concomitant increase in EGR-1 mRNA expression in the LA induced by fear conditioning. Rats administered systemic diazepam before fear conditioning displayed both anxiolytic effects during the post-shock period and amnesic effects during a retention test 24 h later. Diazepam blocked the fear-conditioning-induced increase in EGR-1 expression in the LA. In addition, diazepam significantly increased EGR-1 mRNA expression in the central nucleus of the amygdala (CeA) in a dose-dependent manner. The results reveal differential regulation of EGR-1 by diazepam in the central and lateral nuclei of the amygdala suggesting that these two amygdala nuclei act in a reciprocal manner during the anxiolytic and amnesic action of the benzodiazepine agonist.

Amygdala↗
PubMed1998

Time course of chronic diazepam effects on the auditory evoked potential of the rat.

The time course of chronic diazepam effects on auditory evoked potentials was studied in rats. Auditory evoked potentials were elicited by background and target tones in a passive oddball paradigm. Diazepam was administered by slow release implants to establish constant blood concentrations. Recordings were made during 21 days of treatment and 9 days after treatment ceased. Diazepam increased the amplitude of the P40 component and decreased the amplitude of the P72-P102 components elicited by background tones. Diazepam increased the amplitude of the P40-P48 component and decreased that of the N58 component elicited by target tones. These effects remained constant during treatment. Diazepam further decreased the amplitude of the P102 component elicited by target tones. This effect became more distinct over time. No group differences were found 9 days after treatment. The constant drug effects on middle-latency components (P40-P48) might reflect diazepam-induced changes in sensory information processing. The decreased long-latency component (P102) might reflect a diminished attention to, or discrimination of, target tones. The time course of this effect might reflect diazepam-enhanced habituation.

Animals↗
PubMed1998

Anomalous rectifying properties of 'diazepam-insensitive' GABA(A) receptors.

Studies using recombinant systems indicate that 'diazepam-insensitive' GABA(A) receptors in the central nervous system contain alpha4 and alpha6 subunits while 'diazepam-sensitive' GABA(A) receptors contain alpha1, alpha2, alpha3 and alpha5 subunits. Both native and recombinant diazepam-sensitive GABA(A) receptors typically exhibit large, outwardly rectifying currents. For example, in patch clamp studies, Human Embryonic Kidney (HEK) 293 cells transfected with cDNAs encoding alpha1beta2gamma2 subunits exhibit a rectification ratio (I +60 mV/I -60 mV) of 1.95 +/- 0.21. However, anomalous rectification was observed in recombinant diazepam-insensitive GABA(A) receptors composed of either alpha4beta2gamma2 (rectification ratio, 0.74 +/- 0.09) or alpha6beta2gamma2 (rectification ratio, 0.67 +/- 0.11) subunits. Based on sequence differences between diazepam-sensitive and -insensitive GABA(A) receptor alpha subunits in the vicinity of the putative channel lining, a point mutation was introduced at His273 on the alpha4 subunit. The rectification ratio in cells expressing a mutated alpha4(Asn273)beta2gamma2 receptor increased to 1.92 +/- 0.17. Moreover, mutation of the homologous residue in the alpha1 subunit to histidine reduced the rectification ratio of alpha1(His274)beta2gamma2 to 1.02 +/- 0.12. The affinities of benzodiazepine site ligands at diazepam-sensitive and -insensitive GABA(A) receptors were unaffected by these mutations. Thus, the electrophysiological properties of diazepam-sensitive and -insensitive GABA(A) receptors may be as divergent as their pharmacological characteristics.

Amino Acid Sequence↗
PubMed1998

L-Arginine abolishes the anxiolytic-like effect of diazepam in the elevated plus-maze test in rats.

The involvement of nitrergic mechanisms in the behavioural effects of diazepam in rats was studied in the elevated plus-maze, open-field and rotarod tests. Administration of the nitric oxide (NO) precursor L-arginine (100 mg/kg, i.p.), assumed to increase the synthesis of NO, abolished the anxiolytic-like effect of diazepam (2 mg/kg, i.p.) in the elevated plus-maze, whereas the inactive enantiomer D-arginine (100 mg/kg) did not. Neither diazepam alone nor in combination with L- or D-arginine affected the exploratory activity of animals in the open field. Pretreatment with L-arginine (100 and 200 mg/kg) did not modify the motor impairment of rats after diazepam (3 mg/kg) in the rotarod test. Diazepam (2 mg/kg i.p.) did not inhibit the cortical or hippocampal cytosolic NO synthase activity measured ex vivo by [3H]L-arginine assay. Diazepam was similarly ineffective in in vitro studies at concentrations up to 10 microM. We conclude that a suppression of NO synthase activity may be important in the anxiolytic-like effect of benzodiazepines. However, diazepam does not inhibit NO synthase directly, but may affect NO synthase activity indirectly via some unknown mechanism.

Animals↗
PubMed1990

Double-blind, randomized trial of diazepam versus placebo for prevention of recurrence of febrile seizures.

The aim of this study was to evaluate the efficacy and tolerance of intermittent oral administration of diazepam during hyperthermia for reducing the recurrence of febrile seizure: 185 children, between 8 months and 3 years of age, with a first febrile seizure and normal neurologic development, were randomly assigned in a double-blind fashion to receive orally administered diazepam (0.5 mg/kg, then 0.20 mg/kg, every 12 hours) or placebo, whenever the rectal temperature was more than 38 degrees C. The main criterion of efficacy was the seizure recurrence rate 1 year after the first seizure. The duration of the study was 3 years; eight different centers in France participated. There were 462 febrile episodes and 1000 days with prophylactic treatment. The recurrence rates did not differ between the diazepam group (16%) and the placebo (19.5%) group. The children with recurrent seizures were significantly younger at the time of the first seizure (17 +/- 6.9 months) than children without a recurrent seizure (21 +/- 8.5 months). In children with recurrent seizures, prophylactic treatment was correctly administered to only 1 of 15 children in the diazepam group and to 7 of 18 children in the placebo group. The following were the reasons for this poor cooperation: convulsion being the first manifestation of the fever (seven cases in each group), parents neglecting to give treatment (nine cases), and refusal to take treatment by two children. Side effects were similar in the two groups except for hyperactivity, which was more frequent in the diazepam (138 days) than in the placebo (34 days) group. Intermittent oral administration of diazepam at the onset of fever offered no advantage over placebo in preventing recurrence of seizure. This finding probably reflects a lack of efficacy of the intermittent method rather than of diazepam itself.

Administration, Oral↗
PubMed1995

Effect of acetaminophen and of low intermittent doses of diazepam on prevention of recurrences of febrile seizures.

Acetaminophen and low doses of diazepam were evaluated for the prevention of recurrences of febrile seizures in a placebo-controlled, double-blind trial. Children after their first febrile seizure were assigned to receive either one dose of rectally administered diazepam, and then, after 6 hours, oral doses of 0.2 mg/kg three times a day for the first 2 days if the fever stayed greater than 38.5 degrees C, or a placebo similarly during forthcoming febrile episodes. In addition, each febrile episode was randomly assigned to be treated with acetaminophen or the placebo. Thus four groups were examined for 2 years: patients receiving two kinds of placebo, patients receiving diazepam and a placebo, patients receiving acetaminophen and a placebo, and patients receiving both diazepam and acetaminophen. Of a total of 180 patients (102 boys), 161 were followed for the 2-year period and 157 were seen at the last outpatient examination: 80 in the diazepam group and 77 in the placebo group. The final analysis of the efficacy of the drugs was made on the basis of the data from 153 patients who had had at least one febrile episode during follow-up. There were 641 fever events during this period, and 38 children (21.1%) had 55 recurrences of febrile seizures. Acetaminophen had no effect on the recurrence rate. Seizures recurred at least once in 21 patients (28.4%) receiving diazepam and 17 (21.5%) receiving a placebo (p = 0.4138, log-rank test). The combination of antipyretic agents with anticonvulsant medication did not reduce the recurrence of febrile seizures. Our results show that low doses of acetaminophen or diazepam or both are ineffective for preventing febrile seizures.

Acetaminophen↗
PubMedDate not supplied

Evaluation of 1,1,1-trichloroethane and flurothyl locomotor effects following diazepam treatment in mice.

The abused volatile solvent 1,1,1-trichloroethane (TCE) shares many acute behavioral effects with central nervous system (CNS) depressants; however, demonstration of tolerance to these effects has been difficult. The purpose of the present study was to investigate the development of TCE-induced changes in locomotor activity in mice following repeated injections with diazepam. In the initial concentration-effect curve determinations, diazepam decreased locomotor activity at all doses tested and TCE produced a biphasic effect, increasing locomotor activity at lower concentrations with return to control levels at a high (16,000 ppm) concentration. Flurothyl, a vapor with convulsive properties, had no pronounced effects on locomotor activity at subconvulsant concentrations. Following four daily injections with vehicle or with 10 mg/kg/day diazepam, mice were administered the same concentration of drug/inhalant that they received initially and were retested for locomotor activity effects. Concentration-effect curves for diazepam and flurothyl were not altered by this modest regimen of repeated dosing with diazepam. In contrast, sensitization to the locomotor-stimulating effects of TCE was observed in diazepam-treated mice, but not in vehicle-treated mice. These results suggest that the development of sensitization to TCE involves common mechanisms with those that are affected by repeated dosing with the CNS depressant diazepam.

Animals↗
PubMed2002

Male and female C57BL/6 mice respond differently to diazepam challenge in avoidance learning tasks.

Benzodiazepines (BZ) impair learning and memory performance of animals. The goal of this study was to examine sex differences in the effects of diazepam on learning and memory of C57BL/6 mice in avoidance paradigms. Male and female C57BL/6 mice were tested in the one-way active avoidance, step-down passive avoidance, and foot-shock pain threshold tasks, following administration of vehicle or diazepam (1 mg/kg). No substantial sex or drug effects on the threshold of the pain response to shock were found. There were no significant differences in avoidance performance between vehicle-treated male and female mice while 1 mg/kg of diazepam produced opposite effects on performance of males and females in both tasks. Diazepam-treated females learned faster in the active avoidance task and showed stronger retention in the passive avoidance task. In contrast, diazepam impaired learning of males in the active avoidance task and had no effect on their performance in the passive avoidance task. Diazepam-induced impairment in males was not due to higher sensitivity to the sedative effect of diazepam as females were more sedated than males on the first trial of the passive avoidance task. Our data showed that sedative and amnesic effects of BZs are not tightly linked. This study also suggests that cognitive effects of BZs in rodents could be sex dependent and highlight the importance of using both sexes in studies on behavioral effects of psychoactive drugs.

Animals↗