Dexmedetomidine alleviates ethanol withdrawal symptoms in the rat

Riihioja, Päivi; Jaatinen, Pia; Oksanen, Hanna; Haapalinna, Antti; Heinonen, Esa; Hervonen, Antti

doi:10.1016/s0741-8329(97)00044-x

Cited by 35 publications

(17 citation statements)

References 52 publications

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“…Both pre-and postsynaptic noradrenergic ligands that have the generalized effect of attenuating noradrenergic transmission (with antagonists at postsynaptic receptors or agonists at presynaptic inhibitory autoreceptors) are effective at reducing both the somatic and behavioral symptoms associated with acute withdrawal (Aston-Jones and Harris, 2004; Delfs et al, 2000;Ozdogan et al, 2003;Riihioja et al, 1997a;Riihioja et al, 1997b;Trzaskowska et al, 1986;Van der Laan, 1987). Although prazosin was administered peripherally in the present study, previous evidence has implicated central noradrenergic transmission as participating in withdrawal-induced behavioral changes (Aston-Jones et al, 1999;Aston-Jones and Harris, 2004;Maldonado, 1997).…”

Section: Discussionmentioning

confidence: 80%

“…Although it has been shown previously that norepinephrine depletion produced by blockade of the synthetic pathway attenuates ethanol self-administration in rats Brown et al, 1977;Davis et al, 1978), noradrenergic systems have received much less attention in ethanol-dependence. However, there is evidence suggesting that modulation of noradrenergic systems shows efficacy in alleviating certain aspects of ethanol withdrawal and dependence that could be related to enhanced ethanol consumption (Patkar et al, 2003;Rasmussen et al, 2006;Riihioja et al, 1997a;Riihioja et al, 1997b;Trzaskowska et al, 1986) from a negative reinforcement perspective (i.e., removal of negative stimuli translates into a positive event that is considered reinforcing).…”

Section: Introductionmentioning

confidence: 99%

“…Postsynaptic β-adrenergic antagonists have been shown to reduce withdrawal-induced convulsions (Trzaskowska et al, 1986) and tremors (Riihioja et al, 1997b). Likewise, presynaptic α 2 -noradrenergic receptor agonists have been shown to reduce rigidity, tremor and irritability associated with ethanol withdrawal (Riihioja et al, 1997a;Riihioja et al, 1997b). Additionally, α 1 -adrenergic receptor antagonists have been shown to reduce the locomotor hyperactivity produced by ethanol withdrawal (Trzaskowska et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

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α1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol

Walker

Rasmussen

Raskind

et al. 2008

Alcohol

157

142

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The purpose of this study was to test the hypothesis that blockade of α 1 -adrenergic receptors may suppress the excessive ethanol consumption associated with acute withdrawal in ethanol-dependent rats. Following the acquisition and stabilization of operant ethanol self-administration in male Wistar rats, dependence was induced in half the animals by subjecting them to a four-week intermittent vapor exposure period in which animals were exposed to ethanol vapor for 14 hours per day. Subsequent to dependence induction, the effect of prazosin (0.0, 0.25, 0.5, 1, 1.5 and 2.0 mg/kg IP) was tested on operant responding for ethanol in vapor-exposed and control rats during acute withdrawal. In ethanol-dependent animals, prazosin significantly suppressed responding at the 1.5 and 2.0 mg/kg doses, whereas only the 2.0 mg/kg dose was effective in nondependent animals, identifying an increase in the sensitivity to prazosin in dependent animals. Conversely, at the lowest dose tested (0.25 mg/kg), prazosin increased responding in nondependent animals, which is consistent with the effect of anxiolytics on ethanol self-administration in non-dependent animals. None of the doses tested reliably affected concurrent water self-administration. These results suggest the involvement of the noradrenergic system in the excessive alcohol drinking seen during acute withdrawal in ethanol-dependent rats.

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Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

α1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol

Walker

Rasmussen

Raskind

et al. 2008

Alcohol

157

142

View full text Add to dashboard Cite

show abstract

“…For the acute study, another group of animals (group 5) received a single dose of dexmedetomidine (20 µ g/kg, subcutaneously) on gestation day 19 only to simulate a model of systemic analgesia. The doses and route of dexmedetomidine administration were selected on the basis of an earlier study [19]. The body weight of animals was monitored daily before the administration of the drug.…”

Section: Methodsmentioning

confidence: 99%

Effects of Subchronic versus Acute in utero Exposure to Dexmedetomidine on Foetal Developments in Rats

Tariq

Černý

Elfaki

et al. 2008

Basic Clin Pharma Tox

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Dexmedetomidine is a highly selective and specific α -2 adrenergic agonist with sedative, analgesic and sympathetic activities. This study was undertaken to investigate the effects of in utero exposure of dexmedetomidine on foetal development and postnatal behaviour in the offspring. Pregnant Sprague-Dawley rats were chronically treated with dexmedetomidine (0, 5, 10 and 20 µ g/kg, subcutaneously) daily from gestation day 7 to day 19. Another group of animals received only a single acute dose of dexmedetomidine (20 µ g/kg) on gestational day 19 to mimic a model for systemic analgesia during labour. Administration of dexmedetomidine did not affect the frequency of implantations. Chronic administration of 10 and 20 µ g/kg of dexmedetomidine significantly reduced the body weight and crown-rump length of pups, whereas a single acute dose (20 µ g/kg) did not affect these parameters. None of the pups exhibited any external malformations or skeletal abnormalities irrespective of treatment assigned. All the pups showed a normal postnatal weight gain during the developmental phase. No significant differences were observed among any of the groups with respect to behavioural performances of offspring in beam balance, grip strength and inclined plane tests as well as motor activity. In conclusion, acute exposure to dexmedetomidine at the anticipated delivery time does not exert any adverse effects on perinatal morphology of pups, their birth weight, crown-rump length, physical growth and postnatal behavioural performances. Since this study was conducted in rats, its clinical relevance in human beings remains to be unclear and warrants further studies.

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“…DEX is also known to have a marked interpatient variability when it comes to sedative effects, which is still largely unexplained [27]. Its ability to control shivering has been documented in healthy volunteers subjected to hypothermia and attributed to central inhibition of systemic catecholamine release through N-methyl- D -aspartate (NMDA)-mediated autonomic hyperactivity [28], in a similar way in which it has shown efficacy in controlling tremor related to acute alcohol withdrawal syndrome [29,30,31]. A similar case has been reported with uremic encephalopathy-related tremor, which is also thought to be ultimately caused by increased NMDA activity and catecholamine release [15].…”

Section: Discussionmentioning

confidence: 99%

Factors Associated with Tremor Changes during Sedation with Dexmedetomidine in Parkinson's Disease Surgery

Honorato‐Cia

Martínez-Simón²,

Alegre³

et al. 2015

Stereotact Funct Neurosurg

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Introduction: Dexmedetomidine is an α₂-agonist recently proposed as a potentially ideal drug for sedation during the surgical treatment of Parkinsonʼs disease (PD). This report documents the incidence of changes in motor symptoms (especially tremor) in PD patients sedated with dexmedetomidine for deep brain stimulation or ablation procedures. Methods: We reviewed a retrospective cohort of 22 patients who underwent surgery for PD with dexmedetomidine sedation at a single institution from 2010 to 2014. A logistic regression analysis was performed to analyze possible confounding factors. Results: 14 cases of tremor reduction or suppression were recorded (cumulative incidence: 63.6%; 95% CI: 40.7-82.8). No association could be identified between loading dose, β-blocker use and preoperative total Unified Parkinson's Disease Rating Scale III, with tremor changes. The maintenance dose of dexmedetomidine was higher in patients who did not experience changes [median and range for patients with and without tremor alteration 0.75 (0.2-1.0) and 1.0 µg × kg^-1 × h^-1 (0.7-1.4), respectively; p = 0.021]. Conclusion: Dexmedetomidine provides adequate sedation during surgery for PD, but it might affect motor signs making intraoperative testing difficult or even impossible. Dosage appears not to be the determining factor in motor changes, whose cause remains unclear.

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Dexmedetomidine alleviates ethanol withdrawal symptoms in the rat

Cited by 35 publications

References 52 publications

α1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol

α1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol

Effects of Subchronic versus Acute in utero Exposure to Dexmedetomidine on Foetal Developments in Rats

Factors Associated with Tremor Changes during Sedation with Dexmedetomidine in Parkinson's Disease Surgery

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