The dopamine D1 receptor agonist and D2 receptor antagonist LEK-8829 attenuates reinstatement of cocaine-seeking in rats

Milivojevic, Natasa; Krisch, Igor; Sket, D.; Živin, Marko

doi:10.1007/s00210-004-0937-2

Cited by 14 publications

(10 citation statements)

References 38 publications

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“…It has been reported that the rewarding and reinforcing effects of opiate are, at least partially, mediated by nondopaminergic mechanisms, whereas the incentive to seek opiates due to the release of dopamine [Di Chiara and North, 1992]; The DRD2 has been reported to be related to craving in smoker, alcoholics, and cocaine abuser [Erblich et al, 2005;Heinz et al, 2004;Milivojevic et al, 2004]. Our present data seem to support the view that the DRD2 play an important role in the cue reactivity to environmental heroin-related stimuli.…”

Section: Discussionsupporting

confidence: 90%

The effect of dopamine D2, D5 receptor and transporter (SLC6A3) polymorphisms on the cue‐elicited heroin craving in Chinese

Shao

Zhang

et al. 2006

American J of Med Genetics Pt B

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Heroin dependence is resulted from the interaction between multiple genetic and environmental factors. Subjective craving is considered to be a central phenomenon, which contributes to the continuation of drug use in active abuser and the occurrence of relapse in detoxified abusers. Dopamine pathway has been implicated in the cue-elicited craving for a variety of addictive substances. The objective of this study was to test the hypothesis that heroin addicts carrying specific variants in dopamine-related genes would have higher levels of craving following exposure to a heroin-related cue. Craving induced by a series of exposure to heroin-related cue was assessed in a cohort of Chinese heroin abuser (n = 420) recruited from natural abstinence center at Shanghai. Significantly stronger cue-elicited heroin craving was found in individuals carrying D2 dopamine receptor gene (DRD2) TaqI RFLP A1 allele than the non-carriers (P < 0.001). Furthermore, we did not observed significant association of cue-elicited craving with the nine-repeat allelic variants in dopamine transporter gene (DAT) SLC6A3 and with the dinucleotide repeat polymorphism (DRP) 148bp allele in D5 dopamine receptor gene (DRD5). The results of our study suggest that human dopamine pathway be involved in cue-induced heroin craving, and indicate a potential genetic risk factor for persistent heroin behavior and relapse.

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Section: Discussionsupporting

confidence: 90%

The effect of dopamine D2, D5 receptor and transporter (SLC6A3) polymorphisms on the cue‐elicited heroin craving in Chinese

Shao

Zhang

et al. 2006

American J of Med Genetics Pt B

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“…Previous studies have shown that D 1 agonists reduce cocaine-seeking behavior (De Vries et al, 1999; Milivojevic et al, 2004; Self et al, 1996b), decrease cocaine self-administration (Barrett et al, 2004; Caine et al, 1999), and increased the latency for cue-induced cocaine-seeking behavior (Alleweireldt et al, 2002). In addition, a recent study in D 1 knock-out mice showed that the D 1 receptor is crucial for mediating the reinforcing effects of cocaine (Caine et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Dopamine D1 Receptors in Cocaine Dependence Measured with PET and the Choice to Self-Administer Cocaine

Martínez

Slifstein

Narendran

et al. 2009

Neuropsychopharmacol

127

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Objective The goal of this study was to determine D1 receptor availability in human cocaine dependent (CD) subjects and matched healthy controls (HC). In addition, the cocaine dependent subjects performed cocaine self-administration sessions in order to explore the association between D1 receptor availability and cocaine seeking behavior. Methods 25 cocaine dependent subjects (40 ±4 yrs, 19M/6 F) and 23 matched healthy controls (38 ±4 yrs, 19M/4F) were scanned with PET and the radiotracer [11C]NNC 112. During the cocaine self-administration sessions, cocaine dependent volunteers were given the choice to self-administer cocaine (0, 6, and 12 mg) or to receive a monetary voucher worth $5. D1 receptor availability was measured in the limbic, associative and sensori-motor striatum in addition to cortical brain regions. Results No difference in D1 receptor availability was seen between the two groups. A negative association was seen between D1 receptor BPND in the limbic striatum and the choice for the 6 mg dose of cocaine (r = - 0.47, p = 0.02, corrected for age). Conclusions These results do not support the hypothesis that cocaine dependence is associated with a reduction in D1 receptor availability in the striatum. However, within the cocaine-dependent subjects, low D1 receptor availability in the ventral striatum was associated with the choice to self-administer cocaine, suggesting that low D1 receptor availability may be associated with an increased risk of relapse in cocaine dependence.

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“…Buspirone blocks the discriminative stimulus of the D2 agonist, apomorphine (Kamien and Woolverton, 1990), and attenuates apomorphine-induced aggression and sniffing (Protais et al, 1998; Pruus et al, 2000). Dopamine D2 antagonists reliably prevent cocaine cue- and priming-induced reinstatement (Gal and Gyertyan, 2006; Milivojevic et al, 2004; Schenk and Gittings, 2003) as well as priming-induced reinstatement of amphetamine-rewarded runway responding (Ettenberg, 1990). These studies suggest that buspirone could be exerting its effects on reinstatement via a dopamine D2 mechanism, although it has been postulated that the D2 antagonist-like behavioral effects of buspirone may instead be mediated indirectly by 5-HT 1A receptor activity (Nader and Woolverton, 1994).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of buspirone for attenuating cocaine and methamphetamine reinstatement in rats

Shelton¹,

Hendrick²,

Beardsley³

2013

Drug and Alcohol Dependence

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Background There are no approved pharmacotherapies for preventing psychomotor stimulant relapse. The operant reinstatement model has been suggested as a screen for identifying candidate medications. The present study examined if the anxiolytic buspirone could attenuate reinstatement of extinguished responding in Long-Evans rats that previously self-administered intravenous cocaine or methamphetamine. Methods Rats were trained in 2-h daily sessions to self-administer 0.5 mg/kg cocaine or 0.1 mg/kg methamphetamine infusions followed by 12 days of instrumental extinction. Reinstatement was evoked by 17 mg/kg i.p. cocaine primes or response-contingent cocaine-paired cues in cocaine-reinforced rats, and by 1 mg/kg i.p. methamphetamine primes or response-contingent methamphetamine-paired cues in methamphetamine-reinforced rats. Results Buspirone (1 and 3 mg/kg) significantly (p<0.05) attenuated cocaine cue but not cocaine prime reinstatement. Buspirone (1 and 3 mg/kg) also significantly attenuated methamphetamine cue reinstatement. Buspirone (3 mg/kg) significantly attenuated methamphetamine prime reinstatement. During all reinstatement tests, 3 mg/kg buspirone reduced levels of inactive lever pressing relative to those of vehicle, significantly so during the cocaine cue-induced reinstatement tests. Conclusions Given the complexity of buspirone's neuropharmacology consisting of serotonin 5-HT1A receptor partial agonist activity, and dopamine D2, D3 and D4 receptor antagonist effects, it is uncertain which of these activities or their combination is responsible for the present results. Overall, these results suggest that buspirone may reduce the likelihood of relapse to cocaine and methamphetamine use under some conditions, although this speculation must be interpreted with caution given buspirone's similar potency to attenuate inactive-lever responding.

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The dopamine D1 receptor agonist and D2 receptor antagonist LEK-8829 attenuates reinstatement of cocaine-seeking in rats

Cited by 14 publications

References 38 publications

The effect of dopamine D2, D5 receptor and transporter (SLC6A3) polymorphisms on the cue‐elicited heroin craving in Chinese

The effect of dopamine D2, D5 receptor and transporter (SLC6A3) polymorphisms on the cue‐elicited heroin craving in Chinese

Dopamine D1 Receptors in Cocaine Dependence Measured with PET and the Choice to Self-Administer Cocaine

Efficacy of buspirone for attenuating cocaine and methamphetamine reinstatement in rats

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