Acamprosate decreases the induction of tolerance and physical dependence in morphine-treated mice

Sepúlveda, Jacqueline; Ortega, Andrea; Zapata, Gladys; Contreras, Enrique

doi:10.1016/s0014-2999(02)01767-3

Cited by 15 publications

(7 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Daily morphine injections led to a progressive increase in locomotor activity, with significantly elevated locomotion on days 4 and 7 compared to day 1. A two-factor repeated measures ANOVA shows significant effects of both drug (F (1,28) =211.2, P<0.001) and time of treatment (F (2,28) =6.82, P<0.001) as well as an interaction between the drug and the time of treatment (F (2,28) =7.05, P<0.001). In contrast, no enhancement of locomotor activity was observed in mice injected with saline for 7 days.…”

Section: The Effect Of Atpm-et On Morphine Physical Dependencementioning

confidence: 96%

See 1 more Smart Citation

Effects of ATPM-ET, a novel κ agonist with partial μ activity, on physical dependence and behavior sensitization in mice

Sun

Wang

et al. 2010

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: To investigate the effects of ATPM-ET -N-cyclopropylmethylmorphinan hydrochloride] on physical dependence and behavioral sensitization to morphine in mice. Methods: The pharmacological profile of ATPM-ET was characterized using competitive binding and GTPγS binding assays. We then examined the antinociceptive effects of ATPM-ET in the hot plate test. Morphine dependence assay and behavioral sensitization assay were used to determine the effect of ATPM-ET on physical dependence and behavior sensitization to morphine in mice. Results: The binding assay indicated that ATPM-ET ATPM-ET exhibited a high affinity to both κ-and µ-opioid receptors with K i values of 0.15 nmol/L and 4.7 nmol/L, respectively, indicating it was a full κ-opioid receptor agonist and a partial μ-opioid receptor agonist. In the hot plate test, ATPM-ET produced a dose-dependent antinociceptive effect, with an ED 50 value of 2.68 (2.34-3.07) mg/kg. Administration of ATPM-ET (1 and 2 mg/kg, sc) prior to naloxone (3.0 mg/kg, sc) injection significantly inhibited withdrawal jumping of mice. In addition, ATPM-ET (1 and 2 mg/kg, sc) also showed a trend toward decreasing morphine withdrawal-induced weight loss. ATPM-ET (1.5 and 3 mg/kg, sc) 15 min before the morphine challenge significantly inhibited the morphine-induced behavior sensitization (P<0.05). Conclusion: ATPM-ET may have potential as a therapeutic agent for the treatment of drug abuse.

show abstract

Section: The Effect Of Atpm-et On Morphine Physical Dependencementioning

confidence: 96%

“…However, repeated use of morphine can induce tolerance and addiction (physical and psychological dependence) [1,2] . Indeed, opioid addiction persists as a major public health problem [3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

Effects of ATPM-ET, a novel κ agonist with partial μ activity, on physical dependence and behavior sensitization in mice

Sun

Wang

et al. 2010

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…Mice were subjected to 30 minutes of transient focal cerebral ischemia as described below followed by intraperitoneal treatment with either acamprosate (Sigmal-Aldrich, Taufkirchen, Germany; solved in NaCl) or standard saline (control) during reperfusion, at 3, 6, 9, 12, and 24 hours after stroke. Referring to previous studies, [15][16][17][18][19][20] mice received a modified injection protocol with a single intraperitoneal injection of acamprosate at a dose of 400 mg/kg bodyweight (BW). To exclude toxic side effects of acamprosate after high dosage bolus application, analysis of potential weight loss and blood count analysis was performed 1 day before stroke induction as well as on days 7 and 14 after stroke ( Table 1).…”

Section: Experimental Paradigmmentioning

confidence: 99%

The Indirect NMDAR Antagonist Acamprosate Induces Postischemic Neurologic Recovery Associated with Sustained Neuroprotection and Neuroregeneration

Doeppner

Pehlke

Kaltwasser

et al. 2015

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Cerebral ischemia stimulates N-methyl-D-aspartate receptors (NMDARs) resulting in increased calcium concentration and excitotoxicity. Yet, deactivation of NMDAR failed in clinical studies due to poor preclinical study designs or toxicity of NMDAR antagonists. Acamprosate is an indirect NMDAR antagonist used for patients with chronic alcohol dependence. We herein analyzed the therapeutic potential of acamprosate on brain injury, neurologic recovery and their underlying mechanisms. Mice were exposed to cerebral ischemia, treated with intraperitoneal injections of acamprosate or saline (controls), and allowed to survive until 3 months. Acamprosate yielded sustained neuroprotection and increased neurologic recovery when given no later than 12 hours after stroke. The latter was associated with increased postischemic angioneurogenesis, albeit acamprosate did not stimulate angioneurogenesis itself. Rather, increased angioneurogenesis was due to inhibition of calpain-mediated pro-injurious signaling cascades. As such, acamprosate-mediated reduction of calpain activity resulted in decreased degradation of p35, increased abundance of the pro-survival factor STAT6, and reduced N-terminal-Jun-kinase activation. Inhibition of calpain was associated with enhanced stability of the blood-brain barrier, reduction of oxidative stress and cerebral leukocyte infiltration. Taken into account its excellent tolerability, its sustained effects on neurologic recovery, brain tissue survival, and neural remodeling, acamprosate is an intriguing candidate for adjuvant future stroke treatment.

show abstract

“…With respect to opiate addiction, NMDA receptor antagonists block the development of opiate dependence (Sepulveda et al, 2002;Trujillo and Akil, 1995). A growing body of alcoholism research has emphasized the interplay of opiate antagonists and ethanol, itself an NMDA receptor antagonist (Krystal et al, 2003b).…”

Section: Introductionmentioning

confidence: 99%

Potentiation of Low Dose Ketamine Effects by Naltrexone: Potential Implications for the Pharmacotherapy of Alcoholism

Krystal

Madonick

Perry

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

The interplay of opiate and NMDA glutamate receptors may contribute to psychosis, cognitive function, alcoholism, and substance dependence. Ketamine and ethanol block the NMDA glutamate receptor. The purpose of this randomized double-blind, placebocontrolled human laboratory study was to evaluate whether the interactive effects of drugs acting at opiate and NMDA glutamate receptors might partially explain the efficacy of naltrexone for the treatment of alcoholism, that is, whether naltrexone 25 mg pretreatment would modulate ketamine effects in healthy human subjects. Two groups of healthy subjects were studied. An initial group (n ¼ 31) received a perception-altering subanesthetic dose of ketamine (bolus of 0.23 mg/kg over 1 min followed by a 60-min infusion of 0.58 mg/kg or saline bolus and infusion). A second group (n ¼ 24) completed the same testing procedures, but received a subperceptual ketamine dose (bolus 0.081 mg/kg over 10 min followed by an infusion of 0.4 mg/kg/h). Ketamine produced positive symptoms, negative symptoms, emotional discomfort, and cognitive effects as measured by the Positive and Negative Syndrome Scale (PANSS) in a doserelated fashion. The lower ketamine dose produced subjective effects similar to two standard ethanol drinks, whereas the higher ketamine dose produced effects similar to five standard drinks. Although naltrexone produced no significant behavioral effects, it significantly magnified the increase in the total PANSS score produced by the lower subperceptual dose of ketamine, but not the higher perception-altering dose of ketamine. These data suggest that the interplay of opiate receptor antagonism and NMDA receptor antagonism may be relevant to the protective effects of naltrexone on alcohol consumption via potentiation of dysphoric effects associated with the NMDA receptor antagonist effects of ethanol. However, these data suggest that at levels of NMDA receptor antagonism associated with heavy drinking, this protective effect of naltrexone on drinking is no longer present.

show abstract

Acamprosate decreases the induction of tolerance and physical dependence in morphine-treated mice

Cited by 15 publications

References 20 publications

Effects of ATPM-ET, a novel κ agonist with partial μ activity, on physical dependence and behavior sensitization in mice

Effects of ATPM-ET, a novel κ agonist with partial μ activity, on physical dependence and behavior sensitization in mice

The Indirect NMDAR Antagonist Acamprosate Induces Postischemic Neurologic Recovery Associated with Sustained Neuroprotection and Neuroregeneration

Potentiation of Low Dose Ketamine Effects by Naltrexone: Potential Implications for the Pharmacotherapy of Alcoholism

Contact Info

Product

Resources

About