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Diazepam effects


Discriminative stimulus effects of diazepam in rats evidence for a

6.11.2018 by Thomas Addington
Diazepam effects

J Pharmacol Exp Ther. 1983 Oct;227(1):160-6. Discriminative stimulus effects of diazepam in rats: evidence for a maximal effect. Shannon HE, Herling S.

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Moreover, the dose-effect curves of nine additional benzodiazepine analogs also did not differ markedly in rats trained with either 1.0 or 3.0 mg/kg of diazepam. However, increasing the training dose to 3.0 or 6.0 mg/kg did not result in additional, concomitant shifts in these dose-effect curves. Furthermore, the selective benzodiazepine antagonist CGS8216 blocked the effects of diazepam but not the diazepam-like effects of pentobarbital. Increasing the training dose of diazepam from 0.3 to 1.0 mg/kg resulted in approximay a 3-fold shift to the right in the dose-effect curves for each of these four drugs. These results demonstrate that the discriminative effects of diazepam are qualitatively similar across this 20-fold range of training doses; quantitatively, the discriminative effects of diazepam appear to reach a maximum and plateau above a training dose of 1.0 mg/kg in rats.(ABSTRACT TRUNCATED AT 250 WORDS). The nonbenzodiazepines ethanol, phencyclidine, cyproheptadine and ketocyclazocine failed to produce diazepam-like discriminative stimuli in rats trained with either 0.3, 1.0 or 3.0 mg/kg of diazepam. Rats were trained to discriminate between saline and either 0.3, 1.0, 3.0 or 6.0 mg/kg of diazepam in a two-choice, discrete-trial avoidance procedure. Diazepam, chlordiazepoxide, flurazepam and pentobarbital occasioned dose-related increases in diazepam-appropriate responding in all four training dose groups. In rats trained with 1.0 mg/kg of diazepam, Ro 11-6896, but not its inactive stereoisomer Ro 11-6893, occasioned diazepam-appropriate responding.

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National Library of Medicine 8600 Rockville Pike, Bethesda MD, 20894 USA. National Center for Biotechnology Information, U.S.

Effects of diazepam and midazolam on baroreflex control of heart

3.8.2018 by Thomas Addington
Diazepam effects

Marty J, Gauzit R, Lefevre P, Couderc E, Farinotti R, Henzel C, Desmonts JM. The effects of induction of anesthesia with diazepam and midazolam on baroreflex.

National Library of Medicine 8600 Rockville Pike, Bethesda MD, 20894 USA. National Center for Biotechnology Information, U.S.

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This study also indicates that the depression of arterial baroreflex heart rate responses under diazepam or midazolam anesthesia are less pronounced than the depression of baroreflex responses reported by other investigators with potent inhalational anesthetics. In contrast, epinephrine concentration decreased only after midazolam. The authors conclude that diazepam or midazolam used for induction of anesthesia results in a transient depression of baroreflex function and a sustained decrease of sympathetic tone. The pressor baroreflex slope declined significantly after diazepam or midazolam administration with the maximal changes (-45 and -43%, respectively) observed when plasma diazepam or midazolam concentrations were the highest. The effects of induction of anesthesia with diazepam and midazolam on baroreflex control of heart rate and on plasma levels of catecholamines were investigated in this study. Baroreflex function was assessed using a pressor test (phenylephrine). Group 1 subjects (n = 10) received diazepam, 0.4 mg/kg. Norepinephrine plasma concentrations decreased at each measurement with both drugs. In addition, samples for subsequent determination of plasma norepinephrine and epinephrine levels and plasma diazepam or midazolam concentrations were collected before and 5, 10, and 15 min after intravenous drug administration. Group 2 subjects (n = 10) received midazolam, 0.3 mg/kg. However, this disruptive effect of diazepam and midazolam on sympathetic control of circulation might induce a limited ability to compensate for hemodynamic alterations related to hypovolemia.

Diazepam effects on the exploratory behaviour of rats in an elevated

12.17.2018 by Jason Bawerman
Diazepam effects

Behav Brain Res. 1990 Nov 15;40(2):109-18. Diazepam effects on the exploratory behaviour of rats in an elevated runway: evidence for biphasic effects of.

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National Center for Biotechnology Information, U.S. National Library of Medicine 8600 Rockville Pike, Bethesda MD, 20894 USA.

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In the first experiment, male Sprague-Dawley rats treated with diazepam (2.0 mg/kg, i.p., -30 min) compared to saline-treated animals, increased the time spent exploring the open end of the runway but not the wall end of the runway, thus supporting the fear-reduction model. The initial increase and subsequent decrease in exploration caused by diazepam were encompassed by the biphasic model of BZ action more adequay than either the fear-reduction or reward-enhancement models. In Experiment 2, exploration was rewarded by adding to the open end of the runway a patch of litter soiled by a female rat. This produced a behavioural pattern in naive saline-treated rats very similar to that seen in naive diazepam-treated rats in the first experiment. Instead, they habituated to the novelty of the runway, as grooming and sitting still replaced investigation. However, saline-treated animals, made less fearful by repeated prior exposure to the runway, did not show a similar increase in open-end exploration. According to this hypothesis an animal given a tranquilizer should selectively increase the amount of investigative behaviour in the more novel portion of an elevated maze. The purpose of this study was to test the validity of the fear-reduction model of benzodiazepine (BZ) action on the exploration of novelty. To permit comparison of the same behaviours at both ends of the maze, an elevated runway was built with a wall running lengthwise along the midline of one end. In Experiment 3, diazepam potentiated the habituation of rats previously familiarized with the runway.

Effects of diazepam and its metabolites on nocturnal melatonin

11.16.2018 by Thomas Addington
Diazepam effects

Chronobiol Int. 2003 Mar;20(2):285-97. Effects of diazepam and its metabolites on nocturnal melatonin secretion in the rat pineal and Harderian glands.

We investigated the effects of diazepam (DZP) and its three metabolites: nordiazepam (NZP), oxazepam (OZP), and temazepam (TZP) on pineal gland nocturnal melatonin secretion. We looked at the effects of benzodiazepines on pineal gland melatonin secretion both in vitro (using organ perifusion) and in vivo in male Wistar rats sacrificed in the middle of the dark phase. We also examined the effects of these benzodiazepines on in vivo melatonin secretion in the Harderian glands. Neither DZP M) nor its metabolites M) affected melatonin secretion by perifused rat pineal glands in vitro. In contrast, a 10(-4)M suprapharmacological concentration of DZP increased melatonin secretion of perifused pineal glands by 70%. In vivo, a single acute subcutaneous administration of DZP (3 mg/kg body weight) significantly affected pineal melatonin synthesis and plasma melatonin levels, while administration of the metabolites under the same conditions did not. DZP reduced pineal melatonin content (-40%), N-acetyltransferase activity (-70%), and plasma melatonin levels (-40%), but had no affects on pineal hydroxyindole-O-methyltransferase activity. Neither DZP nor its metabolites affected Harderian gland melatonin content. Our results indicate that the in vivo inhibitory effect of DZP on melatonin synthesis is not due to the metabolism of DZP. The results also show that the control of melatonin production in the Harderian glands differ from that observed in the pineal gland.

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National Center for Biotechnology Information, U.S. National Library of Medicine 8600 Rockville Pike, Bethesda MD, 20894 USA.

Effects of diazepam and flumazenil on minimum alveolar

10.15.2018 by Isaac Mercer
Diazepam effects

Effects of diazepam and flumazenil on minimum alveolar concentrations for dogs anesthetized with isoflurane or a combination of isoflurane and fentanyl.

Fentanyl significantly decreased isoflurane MAC (corrected to a barometric pressure of 760 mm Hg) from 1.80+/-0.21 to 0.85+/-0.14%, a reduction of 53%. Isoflurane-fentanyl-diazepam MAC (0.48+/-0.29%) was significantly less than isoflurane-fentanyl-saline MAC (0.79+/-0.21%). Percentage reduction in isoflurane MAC was significantly greater for fentanyl-diazepam (74%), compared with fentanyl-saline (54%) or fentanyl-flumazenil (61%). Mean fentanyl concentrations for the entire experiment were increased over time and were higher in the diazepam group than the saline or flumazenil groups.

Dogs were anesthetized with isoflurane 3 times during a 6-week period. After a 30-minute equilibration period, each MAC determination was performed in triplicate, using standard techniques. Fentanyl was administered as a bolus (10 microg/kg of body weight, IV) that was followed by a constant infusion (0.3 microg/kg per min, IV) throughout the remainder of the experiment. After determining isoflurane-fentanyl MAC in triplicate, each dog received saline (0.9% NaCl) solution, diazepam, or flumazenil. After 30 minutes, MAC was determined again.

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Fentanyl markedly decreased isoflurane MAC in dogs. Diazepam, but not flumazenil, further decreased isoflurane-fentanyl MAC. Our results indicate that diazepam enhances, whereas flumazenil does not affect, opioid-induced CNS depression and, possibly, analgesia in dogs.

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8 mixed-breed adult dogs.

To determine the effect of a constant-rate infusion of fentanyl on minimum alveolar concentration (MAC) of isoflurane and to determine the interaction between fentanyl and a benzodiazepine agonist (diazepam) and antagonist (flumazenil) in isoflurane-anesthetized dogs.