Levo-tetrahydropalmatine attenuates oxycodone-induced conditioned place preference in rats

Li, Yanli; Yan, Lingdi; Peilan, Zhou; Wu, Chunfu; Gong, Ze‐Hui

doi:10.1016/j.ejphar.2008.11.031

Cited by 46 publications

(24 citation statements)

References 35 publications

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“…However, in both cases, these effects, which potentially reflect anhedonia, emerged at doses higher than those at which effects on responses to cocaine were observed and may have been related to motor impairment. Further, l -THP, at doses as high as 18.5 mg/kg (ip), does not produce conditioned place aversion (Liu et al, 2009) and anxiogenic effects of l -THP have not been reported. In fact, racemic (dl) THP has been reported to have anxiolytic properties (Leung et al, 2003) and l -THP containing preparations are often used for their sedative effects.…”

Section: Discussionmentioning

confidence: 99%

Oral administration of levo-tetrahydropalmatine attenuates reinstatement of extinguished cocaine seeking by cocaine, stress or drug-associated cues in rats

Figueroa-Guzman

Mueller

Vranjkovic

et al. 2011

Drug and Alcohol Dependence

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Cocaine addiction is characterized by a persistently heightened susceptibility to drug relapse. For this reason, the identification of medications that prevent drug relapse is a critical goal of drug abuse research. Drug re-exposure, the onset of stressful life events, and exposure to cues previously associated with drug use have been identified as determinants of relapse in humans and have been found to reinstate extinguished cocaine seeking in rats. This study examined the effects of acute oral (gavage) administration of levo-tetrahydropalmatine (l-THP), a tetrahydroprotoberberine isoquinoline with a pharmacological profile that includes antagonism of D1, D2 and D3 dopamine receptors, on the reinstatement of extinguished cocaine seeking by a cocaine challenge (10 mg/kg, ip), a stressor (uncontrollable electric footshock [EFS]) or response-contingent exposure to a stimulus (tone and light complex) previously associated with drug delivery in male Sprague-Dawley rats. Extinguished drug seeking was reinstated by ip cocaine, EFS, or response-contingent presentation of drug-associated cues in vehicle-pretreated rats following extinction of iv cocaine self-adminisration. Oral administration of either 3.0 or 10.0 mg/kg l-THP one hour prior to reinstatement testing significantly attenuated reinstatement by each of the stimuli. Food-reinforced responding and baseline post-extinction responding were significantly attenuated at the 10.0, but not the 3.0 mg/kg, l-THP dose, indicating that the effects of 3 mg/kg l-THP on reinstatement were likely independent of non-specific motor impairment. These findings further suggest that l-THP may have utility for the treatment of cocaine addiction.

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Section: Discussionmentioning

confidence: 99%

Oral administration of levo-tetrahydropalmatine attenuates reinstatement of extinguished cocaine seeking by cocaine, stress or drug-associated cues in rats

Figueroa-Guzman

Mueller

Vranjkovic

et al. 2011

Drug and Alcohol Dependence

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“…Indeed, clinical trials demonstrating efficacy in recovering heroin addicts [57, 58] along with studies showing efficacy in preclinical models of opiate abuse [62] suggest that l -THP may be effective for treating addiction to heroin. Studies examining its potential use in other addiction populations (alcohol, nicotine) are currently ongoing and should provide additional understanding about the therapeutic utility of l -THP in the near future.…”

Section: Future Perspectivementioning

confidence: 99%

L -Tetrahydropalamatine: A Potential New Medication for the Treatment of Cocaine Addiction

Wang

Mantsch

2012

Future Med. Chem.

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Levo-tetrahydropalmatine (l-THP) is an active constituent of herbal preparations containing plant species of the genera Stephania and Corydalis and has been approved and used in China for a number of clinical indications under the drug name Rotundine. The pharmacological profile of l-THP, which includes antagonism of dopamine D1 and D2 receptors and actions at dopamine D3, alpha adrenergic and serotonin receptors, suggests that it may have utility for treating cocaine addiction. In this review, we provide an overview of the pharmacological properties of l-THP and the evidence supporting its development as an anti-addiction medication. The results of preclinical work demonstrating that l-THP attenuates cocaine’s reinforcing/rewarding effects and reinstatement in rat models of cocaine relapse are summarized, and the outcomes of studies demonstrating efficacy in human addicts are described. Finally, an overview of the safety profile of l-THP is provided and challenges associated with FDA approval of l-THP are discussed.

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“…Previous studies as well as the present study have shown that morphine (4.0 mg/kg, s.c.), oxycodone (0.56 mg/kg, s.c.), and fentanyl (0.017 mg/kg) produce a significant place preference in naïve rats (12,28,29).…”

Section: Rewarding Effects Of Opioids On Paclitaxel-and Oxaliplatininmentioning

confidence: 99%

Establishment of Opioid-Induced Rewarding Effects Under Oxaliplatin- and Paclitaxel-Induced Neuropathy in Rats

et al. 2014

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IntroductionAlthough m-opioid receptor agonists such as morphine, oxycodone, and fentanyl have prominent antinociceptive effects, they also have adverse effects (e.g., emesis, constipation, drowsiness, and psychological dependence). Psychological dependence on opioids is a serious problem worldwide, and one of the triggers for inducing such opioid dependence is the inappropriate use or overdose of prescribed m-opioid receptor agonists (1). It is widely accepted that psychological events such as the reinforcing effects induced by m-opioid receptor agonists can be mimicked in animals as rewarding effects (2 -4), and activation of the mesolimbic dopaminergic system, which projects from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), plays an important role in the rewarding effects of m-opioid receptor agonists (5 -8).Recently, it has been shown that, as long as m-opioid receptor agonists are used appropriately to control pain, psychological dependence does not occur in clinical situations (9,10 Abstract. The rewarding effects of m-receptor agonists can be suppressed under several pain conditions. We recently showed that clinically used m-receptor agonists possess efficacies for relieving the neuropathic pain induced by chemotherapeutic drug in rats; however, it is possible that the use of m-receptor agonists may trigger the rewarding effects even under chemotherapeutic drug-induced neuropathic pain. Nevertheless, no information is available regarding whether mreceptor agonists produce psychological dependence under chemotherapeutic drug-induced neuropathic pain. Therefore, we examined the effects of neuropathy induced by chemotherapeutic drugs on the rewarding effects of morphine, oxycodone, and fentanyl in rats. Repeated treatment with oxaliplatin or paclitaxel produced neuropathy as measured by the von Frey test. Rewarding effects produced by antinociceptive doses of m-receptor agonists were not suppressed under oxaliplatin-or paclitaxel-induced neuropathy. Furthermore, the morphine-induced increase in the release of dopamine from the nucleus accumbens, which is a critical step in the rewarding effects of m-receptor agonists, was not altered in paclitaxel-treated rats. These results suggest that the rewarding effects of m-receptor agonists can still be established under oxaliplatin-or paclitaxelinduced neuropathic pain. Therefore, patients should be carefully monitored for psychological dependence on m-receptor agonists when they are used to control chemotherapeutic drug-induced neuropathic pain.

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Levo-tetrahydropalmatine attenuates oxycodone-induced conditioned place preference in rats

Cited by 46 publications

References 35 publications

Oral administration of levo-tetrahydropalmatine attenuates reinstatement of extinguished cocaine seeking by cocaine, stress or drug-associated cues in rats

Oral administration of levo-tetrahydropalmatine attenuates reinstatement of extinguished cocaine seeking by cocaine, stress or drug-associated cues in rats

L -Tetrahydropalamatine: A Potential New Medication for the Treatment of Cocaine Addiction

Establishment of Opioid-Induced Rewarding Effects Under Oxaliplatin- and Paclitaxel-Induced Neuropathy in Rats

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