Attenuation of ethanol self-administration and of conditioned reinstatement of alcohol-seeking behaviour by the antiopioid peptide nociceptin/orphanin FQ in alcohol-preferring rats

Ciccocioppo, Roberto; Economidou, Daina; Fedeli, Amalia; Angeletti, Stefania; Weiss, Friedbert; Heilig, Markus; Massi, Maurizio

doi:10.1007/s00213-003-1645-1

Cited by 161 publications

(156 citation statements)

References 58 publications

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“…Both approaches 'Anti-alcohol' effects of Ro 64-6198 A Kuzmin et al demonstrated that the effects of Ro 646198 are selective for the ADE. The effects of nociceptin (Ciccocioppo et al, 1999(Ciccocioppo et al, , 2004Martin-Fardon et al, 2000;Kuzmin et al, 2003) and Ro 64-6198 (present study) on alcohol intake may be mediated through several neurotransmitter systems. The dopamine (DA) and opioid systems regulating ethanol-related behaviors may be involved.…”

Section: Discussionmentioning

confidence: 59%

“…Thus, nociceptin injected intracerebroventricularly (i.c.v.) modified ethanol intake and inhibited ethanol-seeking behavior in rats trained for ethanol selfadministration (Ciccocioppo et al, , 2004. This peptide also reduced the effects of footshock stress on ethanolseeking behavior (Martin-Fardon et al, 2000).…”

Section: Introductionmentioning

confidence: 92%

“…Several studies have demonstrated that the endogenous nociceptin/opioid receptor-like 1 (ORL-1) receptor system is involved in the rewarding effects of ethanol (Ciccocioppo et al, 1999(Ciccocioppo et al, , 2004Martin-Fardon et al, 2000;Kuzmin et al, 2003). Thus, nociceptin injected intracerebroventricularly (i.c.v.)…”

Section: Introductionmentioning

confidence: 99%

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The Nociceptin/Orphanin FQ Receptor Agonist Ro 64-6198 Reduces Alcohol Self-Administration and Prevents Relapse-Like Alcohol Drinking

Kuzmin

Kreek

Bakalkin

et al. 2006

Neuropsychopharmacol

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Effects of the opioid receptor like-1 (ORL-1) receptor agonist Ro 64-6198 (0.1, 0.3, and 1.0 mg/kg intraperitoneally (i.p.)) on operant ethanol self-administration and activation of self-administration by ethanol deprivation were studied in male Wistar rats. Acute administration of Ro 64-6198 caused a dose-dependent reduction of ethanol self-administration. In comparison, the opioid antagonist naltrexone (0.1, 0.3, and 1.0 mg/kg i.p.) inhibited ethanol self-administration at all doses tested. Ethanol deprivation for 10 days significantly increased ethanol self-administration during the first 2 days after deprivation. Daily pretreatment with Ro 64-6198 (0.3 mg/kg) or naltrexone (0.3 mg/kg) during the last 3 days of ethanol deprivation abolished the deprivation-induced increase in ethanol intake. Thus, stimulation of the ORL-1 receptors by Ro 64-6198 reduced the acute reinforcing effects of ethanol and prevented relapse-like behavior in the ethanol-deprivation model in a similar manner as a blockade of opioid receptors by naltrexone. Ro 64-6198 at 0.1 and 0.3 mg/kg doses did not alter self-administration of 0.2% saccharin solution, indicating an apparent selectivity of this compound in modification of ethanol reward. These findings add further support to the idea that Ro 64-6198 and potentially other synthetic ORL-1 receptor agonists are as effective as naltrexone in blocking the actions of ethanol important for its addictive potential in animal experiments, and therefore may have therapeutic value in the treatment of alcoholism. Neuropsychopharmacology (2007) 32, 902-910.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 92%

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The Nociceptin/Orphanin FQ Receptor Agonist Ro 64-6198 Reduces Alcohol Self-Administration and Prevents Relapse-Like Alcohol Drinking

Kuzmin

Kreek

Bakalkin

et al. 2006

Neuropsychopharmacol

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“…For each of the first four alcohol deliveries, the ratio was increased by 1; for the next four deliveries, the ratio was increased by 2; for all the following deliveries, the ratio was increased by 4. Each alcohol-reinforced response resulted in a 1.0-s illumination of the house light, while sessions were terminated when more than 30 min had elapsed since the last reinforced response (Ciccocioppo et al 2004). URB597 1.0 mg/kg or vehicle was given 30 min before starting the operant conditioning experiment.…”

Section: Alcohol Self-administrationmentioning

confidence: 99%

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

et al. 2008

Self Cite

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Rationale A major clinical concern with the use of cannabinoid receptor 1 (CB1) direct agonists is that these compounds increase alcohol drinking and drug abuserelated behaviours. As an alternative approach, CB1-receptor-mediated activity can be facilitated by increasing anandamide levels with the use of hydrolase fatty acid amide hydrolase (FAAH) inhibitors. Objective Using the selective FAAH inhibitor URB597, we investigated whether activation of the endogenous cannabinoid tone increases alcohol abuse liability, as what happens with the CB1 receptor direct agonists.Materials and methods URB597 was tested on alcohol self-administration in Wistar rats and on homecage alcohol drinking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. In Wistar rats, URB597 effects on alcohol-induced anxiety and on stress-, yohimbineand cue-induced reinstatement of alcohol seeking were also evaluated. For comparison, the effect of the CB1 receptor antagonist rimonabant on ethanol self-administration was also tested. Results Under our experimental condition, intraperitoneal (IP) administration of URB597 (0.0, 0.3 and 1.0 mg/kg) neither increased voluntary homecage alcohol drinking in msP rats nor facilitated fixed ratio 1 and progressive ratio alcohol self-administration in nonselected Wistars. In the reinstatement tests, the compound did not have effects on cue-, footshock stress-and yohimbine-induced relapse. Conversely, URB597 completely abolished the anxiogenic response measured during withdrawal after an acute IP administration of alcohol (3.0 g/kg). Rimonabant (0.0, 0.3, 1.0 and 3.0 mg/kg) significantly reduced ethanol self-administration. Conclusions Results demonstrate that activation of the endocannabinoid anandamide system by selective inhibition of FAAH does not increase alcohol abuse risks but does reduce anxiety associated to alcohol withdrawal. We thus can speculate that medication based on the use of endocannabinoid system modulators such as URB597 may offer important advantages compared to treatment with direct CB1 receptor activators.

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“…Utilization of the sucrose-fading procedure to obtain reliable bar pressing for ingestion of alcohol is a popular apvproach to investigate alcohol drinking (Brown et al 1998;Ciccocioppo et al 2004;Lê et al 1999Lê et al , 2003Rogowski et al 2003;Roberts et al 1996;Samson 1986;Valdez et al 2002;Weiss et al 1993). However, while extended absence from bar pressing increased intake when alcohol was restored in some investigations (i.e., similar to alcohol deprivation; Heyser et al 1997;Hölter et al 1997;McKinzie et al 1998), Samson and Chappell (2001) found no effect of deprivation on intake using a limited access operant procedure.…”

Section: Repeated Alcohol Withdrawals and The Alcohol-deprivation Effmentioning

confidence: 99%

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

2004

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Rationale-The rationale for proposing the "kindling"/stress hypothesis is to provide a conceptual basis for the insidious development and maintenance of alcohol abuse.Objective and results-An objective of the hypothesis is to emphasize how continued alcohol abuse is linked to progressive neural adaptation. Work has shown that repeated withdrawals from chronic low levels of alcohol sensitize ("kindle") anxiety-like behavior ("anxiety") in rats, a finding consistent with multiple withdrawal kindling of seizure activity. Additionally, stress substitutes for initial cycles of the multiple withdrawal protocol to sensitize withdrawal-induced anxiety, which is indicative that stress is capable of facilitating neuroadaptive processes related to withdrawal. The persistence of adaptation caused by stress and multiple withdrawals is revealed by the appearance of withdrawal-induced anxiety following a future re-exposure to a single 5-day period of alcohol. This persisting adaptation also permits stress to induce anxiety during a period of abstinence-a response not observed in animals without previous exposure to alcohol. Furthermore, stress interacts with repeated withdrawals to enhance voluntary alcohol drinking. Results of other preclinical and clinical studies reported in the literature are integrated with these investigations in support of the proposed hypothesis.Conclusions-The "kindling"/stress hypothesis is based on the premise that repeated withdrawals from cycles of chronic alcohol exposure contribute to a progressive development of persisting adaptive change that sensitizes withdrawal-induced anxiety and allows stress to evoke symptoms associated with negative affect during abstinence. Thus, these consequences of repeated withdrawals account for the evolution of major characteristics of alcoholism, which include worsened acute withdrawal symptoms and increased stress-induced negative affect during abstinence, both of which enhance the likelihood of relapse-and with relapse an inability to limit an abusive pattern of alcohol intake. The "kindling"/stress hypothesis provides a clear strategy for future studies to explore the advancing neural adaptation proposed to contribute to the pathogenesis of alcoholism.

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Attenuation of ethanol self-administration and of conditioned reinstatement of alcohol-seeking behaviour by the antiopioid peptide nociceptin/orphanin FQ in alcohol-preferring rats

Cited by 161 publications

References 58 publications

The Nociceptin/Orphanin FQ Receptor Agonist Ro 64-6198 Reduces Alcohol Self-Administration and Prevents Relapse-Like Alcohol Drinking

The Nociceptin/Orphanin FQ Receptor Agonist Ro 64-6198 Reduces Alcohol Self-Administration and Prevents Relapse-Like Alcohol Drinking

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

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