Daidzein modulates cocaine-reinforcing effects and cue-induced cocaine reinstatement in CD-1 male mice

ABSTRACT Rationale Cocaine addiction is a chronic relapsing disorder that lacks of an effective treatment. Isoflavones are a family of compounds present in different plants and vegetables like soybeans that share a common chemical structure. Previous studies have described that synthetic derivatives from the natural isoflavone daidzin can modulate cocaine addiction, by a mechanism suggested to involve aldehyde-dehydrogenase (ALDH) activities. Objectives Based on these previous studies, we investigated the effects of three natural isoflavones, daidzin, daidzein, and genistein, on the modulation of the cocaine reinforcing effects and on cue-induced reinstatement in an operant mouse model of cocaine self-administration. Results Chronic treatment with daidzein or genistein decreased operant responding to obtain cocaine intravenous infusions. On the other hand, daidzein and daidzin, but not genistein, were effective in decreasing cue-induced cocaine reinstatement. Complementary studies revealed that daidzein effects on cocaine reinforcement were mediated through a mechanism that involved dopamine type-2/3 receptors (DA-D2/3) activities. Conclusions Our results suggest that these natural compounds alone or in combination can be a potential therapeutic approach for cocaine addiction. Further clinical studies are required in order to ascertain their potential therapeutic use.

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Modification of cocaine self-administration by buspirone (buspar®): potential involvement of D3 and D4 dopamine receptors

The International Journal of Neuropsychopharmacology ◽

10.1017/s1461145712000661 ◽

2012 ◽

Vol 16 (2) ◽

pp. 445-458 ◽

Cited By ~ 66

Author(s):

Jack Bergman ◽

Rebecca A. Roof ◽

Cheryse A. Furman ◽

Jennie L. Conroy ◽

Nancy K. Mello ◽

...

Keyword(s):

Radioligand Binding ◽

Partial Agonist ◽

D2 Receptor ◽

Abuse Liability ◽

Cocaine Addiction ◽

Dose Effect ◽

Self Administration ◽

Binding Studies ◽

High Affinity ◽

Reinforcing Effects

Abstract Converging lines of evidence indicate that elevations in synaptic dopamine levels play a pivotal role in the reinforcing effects of cocaine, which are associated with its abuse liability. This evidence has led to the exploration of dopamine receptor blockers as pharmacotherapy for cocaine addiction. While neither D1 nor D2 receptor antagonists have proven effective, medications acting at two other potential targets, D3 and D4 receptors, have yet to be explored for this indication in the clinic. Buspirone, a 5-HT1A partial agonist approved for the treatment of anxiety, has been reported to also bind with high affinity to D3 and D4 receptors. In view of this biochemical profile, the present research was conducted to examine both the functional effects of buspirone on these receptors and, in non-human primates, its ability to modify the reinforcing effects of i.v. cocaine in a behaviourally selective manner. Radioligand binding studies confirmed that buspirone binds with high affinity to recombinant human D3 and D4 receptors (∼98 and ∼29 nm respectively). Live cell functional assays also revealed that buspirone, and its metabolites, function as antagonists at both D3 and D4 receptors. In behavioural studies, doses of buspirone that had inconsistent effects on food-maintained responding (0.1 or 0.3 mg/kg i.m.) produced a marked downward shift in the dose–effect function for cocaine-maintained behaviour, reflecting substantial decreases in self-administration of one or more unit doses of i.v. cocaine in each subject. These results support the further evaluation of buspirone as a candidate medication for the management of cocaine addiction.

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Faculty Opinions recommendation of The active heroin metabolite 6-acetylmorphine has robust reinforcing effects as assessed by self-administration in the rat.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734678533.793555031 ◽

2019 ◽

Author(s):

M Foster Olive

Keyword(s):

Self Administration ◽

Reinforcing Effects

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Assessment of Acute Motor Effects and Tolerance Following Self‐Administration of Alcohol and Edible ∆ 9 ‐Tetrahydrocannabinol in Adolescent Male Mice

Alcoholism Clinical and Experimental Research ◽

10.1111/acer.14197 ◽

2019 ◽

Vol 43 (11) ◽

pp. 2446-2457

Author(s):

Michael P. Smoker ◽

Maribel Hernandez ◽

Yanping Zhang ◽

Stephen L. Boehm

Keyword(s):

Adolescent Male ◽

Male Mice ◽

Self Administration ◽

Motor Effects

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Hypoglycemic effects of Auricularia auricula polysaccharides on high fat diet and streptozotocin-induced diabetic mice using metabolomics analysis

Food & Function ◽

10.1039/d1fo02022f ◽

2021 ◽

Author(s):

nannan liu ◽

Xuefeng Chen ◽

Juanna Song ◽

Mengyin Chen ◽

Pin Gong ◽

...

Keyword(s):

Diabetes Mellitus ◽

High Fat Diet ◽

Diabetic Mice ◽

Male Mice ◽

High Fat ◽

Auricularia Auricula ◽

Ultrahigh Performance Liquid Chromatography ◽

Metabolomic Approach ◽

Metabolomics Analysis

This study evaluated the hypoglycemic effect of Auricularia auricula polysaccharides (AAPs) on streptozotocin-induced type 2 diabetes mellitus (T2DM) male mice (C57BL/6J) using a metabolomic approach based on ultrahigh-performance liquid chromatography–Q...

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Impact of Morphine Dependence and Withdrawal on the Reinforcing Effectiveness of Fentanyl, Cocaine, and Methamphetamine in Rats

Frontiers in Pharmacology ◽

10.3389/fphar.2021.691700 ◽

2021 ◽

Vol 12 ◽

Author(s):

Robert W. Seaman Jr ◽

Gregory T. Collins

Keyword(s):

Opioid Dependence ◽

Progressive Ratio ◽

Morphine Dependence ◽

Sprague Dawley ◽

Self Administration ◽

Stimulant Use ◽

Concurrent Use ◽

Reinforcing Effects ◽

The Individual ◽

The Impact

Recent estimates suggest increased popularity of the concurrent use of opioids and stimulants, with over 50% of treatment-seeking opioid users reporting regular stimulant use. The goal of the current study was to determine how opioid dependence and withdrawal affect the reinforcing effects of fentanyl, cocaine, and methamphetamine. Male Sprague-Dawley rats were allowed to self-administer fentanyl under a progressive ratio (PR) schedule of reinforcement. Baseline evaluations of reinforcing effectiveness of fentanyl, cocaine, and methamphetamine were determined. Opioid dependence was then established by administering escalating doses of morphine (10–40 mg/kg) twice-daily for four days and subsequently maintained by once-daily injections of 40 mg/kg morphine. To evaluate the impact of opioid dependence and withdrawal on the self-administration of fentanyl, cocaine, and methamphetamine, sessions occurred either 12 or 20 h after the morphine, respectively. During opioid withdrawal, the fentanyl dose-response curve was shifted rightward with an increase in maximal effectiveness, whereas it was shifted rightward with a reduction in maximal effectiveness when evaluated in rats currently dependent on opioids, relative to baseline. The reinforcing effects of cocaine and methamphetamine were unchanged by either condition. The current studies provide direct evidence that the reinforcing effects of fentanyl are increased in opioid-withdrawn rats and reduced in opioid-dependent rats, relative to rats that are not physically dependent on opioids. These findings suggest that motivations to use opioids are dependent on the state of the individual whereas stimulants retain their reinforcing effects regardless of whether the individual is in an opioid-dependent or withdrawn state.

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