The CRF1 receptor antagonist antalarmin attenuates yohimbine-induced increases in operant alcohol self-administration and reinstatement of alcohol seeking in rats

Marinelli, Peter W.; Funk, Douglas; Juzytsch, Walter; Harding, Stephen E.; Rice, Kenner C.; Shaham, Yavin; Lê, A. D.

doi:10.1007/s00213-007-0905-x

Cited by 175 publications

(219 citation statements)

References 90 publications

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“…However, it has been shown that the progesterone metabolite, allopregnanolone, can have both a stimulatory or inhibitory effect on ethanol intake depending on the dose administered and the drinking paradigm used (Ford et al, 2005;Janak et al, 1998;Morrow et al, 2001). Our group and others (Marinelli et al, 2007) have previously shown that yohimbine produces significant increases in circulating CORT levels and, in the present study, we show that yohimbine administration in ethanol-extinguished rats causes a nonsignificant increase in progesterone levels (Supplementary Figure 1). However, the levels in the male rats described here remain very low and are quite close to basal levels reported in the literature (Andersen et al, 2004(Andersen et al, , 2005Auger et al, 2006).…”

Section: Discussionsupporting

confidence: 80%

“…We also found that the high dose of mifepristone can block yohimbine-induced reinstatement of sucrose-seeking when delivered systemically, but not into the CeA. It has previously been shown that yohimbineinduced reinstatement of ethanol-seeking can be modulated by many receptors, including: CRF (Marinelli et al, 2007), orexin (Richards et al, 2008), serotonin (Le et al, 2009), neuropeptide Y (Cippitelli et al, 2010), peroxisome proliferator-activated receptor-g (Stopponi et al, 2011), adrenoreceptors (Le et al, 2011), and delta-opioid receptors (Nielsen et al, 2011). This study is the first, to our knowledge, to indicate that GRs play a role in the reinstatement behavior elicited by yohimbine.…”

Section: Discussionsupporting

confidence: 60%

“…Statistical analysis of inactive lever pressing using a twoway ANOVA revealed an overall effect of yohimbine dose (0 or 2 mg/kg) (F(1,47) ¼ 9.06, po0.01; Table 1), but no effect of pretreatment dose of mifepristone or interaction between mifepristone dose Â yohimbine dose. Yohimbineinduced increases in inactive lever presses have been reported in the literature (Le et al, 2011;Marinelli et al, 2007); however, these effects are inconsistent as our group and others have failed to find such an effect (Le et al, 2005;Nielsen et al, 2011;Richards et al, 2008). More evidence of this inconsistency is offered in this study, where we show that inactive lever responding is increased only in the animals trained to respond for 10% ethanol, and not 20% ethanol or 5% sucrose.…”

Section: Effect Of Mifepristone On Yohimbine-induced Reinstatement Ofcontrasting

confidence: 53%

“…It has been previously shown that these increases are modulated by extrahypothalamic mechanisms, specifically CRF (Marinelli et al, 2007) and serotonin systems (Le et al, 2009). These investigators have demonstrated that serotonin and CRF systems interact within the MRN to modulate reinstatement to ethanol-seeking (Le et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Mifepristone in the Central Nucleus of the Amygdala Reduces Yohimbine Stress-Induced Reinstatement of Ethanol-Seeking

Simms

Haass‐Koffler

Bito-Onon

et al. 2011

Neuropsychopharmacol

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Chronic ethanol exposure leads to dysregulation of the hypothalamic-pituitary-adrenal axis, leading to changes in glucocorticoid release and function that have been proposed to maintain pathological alcohol consumption and increase vulnerability to relapse during abstinence. The objective of this study was to determine whether mifepristone, a glucocorticoid receptor antagonist, plays a role in ethanol self-administration and reinstatement. Male, Long-Evans rats were trained to self-administer either ethanol or sucrose in daily 30 min operant self-administration sessions using a fixed ratio 3 schedule of reinforcement. Following establishment of stable baseline responding, we examined the effects of mifepristone on maintained responding and yohimbine-induced increases in responding for ethanol and sucrose. Lever responding was extinguished in separate groups of rats and animals were tested for yohimbine-induced reinstatement and corticosterone release. We also investigated the effects of local mifepristone infusions into the central amygdala (CeA) on yohimbine-induced reinstatement of ethanol-and sucrose-seeking. In addition, we infused mifepristone into the basolateral amygdala (BLA) in ethanol-seeking animals as an anatomical control. We show that both systemic and intra-CeA (but not BLA) mifepristone administration suppressed yohimbine-induced reinstatement of ethanol-seeking, while only systemic injections attenuated sucroseseeking. In contrast, baseline consumption, yohimbine-induced increases in responding, and circulating CORT levels were unaffected. The data indicate that the CeA plays an important role in the effects of mifepristone on yohimbine-induced reinstatement of ethanolseeking. Mifepristone may be a valuable pharmacotherapeutic strategy for preventing relapse to alcohol use disorders and, as it is FDA approved, may be a candidate for clinical trials in the near future.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 60%

Section: Effect Of Mifepristone On Yohimbine-induced Reinstatement Ofcontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

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Mifepristone in the Central Nucleus of the Amygdala Reduces Yohimbine Stress-Induced Reinstatement of Ethanol-Seeking

Simms

Haass‐Koffler

Bito-Onon

et al. 2011

Neuropsychopharmacol

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“…In addition, Yohimbine, which provokes stress-and anxiety-like behaviors in both humans and rodents, increased operant ethanol self-administration. Yohimbine-induced reinstatement of alcohol seeking was attenuated by the corticotrotropin-releasing factor 1 (CRF1) receptor antagonist antalarmin (Marinelli et al 2007). More importantly, preclinical evidence with pharmacological therapies targeting CRF receptor (CRF-R) signaling were involved in the regulation of neurobiological responses to ethanol; CRF-R antagonists protect against increased ethanol intake and relapse-like behaviors precipitated by exposure to a stressful event [for review see Lowery and Thiele 2010].…”

Section: Consequences Of Csc On Body Weight Gain and Anxiety-like Behmentioning

confidence: 99%

Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice

Bahí

Dreyer

2013

Psychopharmacology

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Rationale We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Objective Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. Methods Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7 days of extinction trials before the 19 days of chronic stress. Druginduced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol. Results Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Conclusion Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

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The role of kappa opioid receptors in stress‐induced reinstatement of alcohol seeking in rats

2014

Self Cite

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IntroductionStress is related to heavy alcohol use and relapse in alcoholics. Using the reinstatement model, we have shown that corticotropin-releasing factor (CRF) underlies stress-induced relapse to alcohol seeking in laboratory rodents. Little is known about how other neurotransmitters interact with CRF in these effects. Dynorphin and its receptor (kappa opioid receptor, KOR) are involved in stress responses and in alcohol seeking. KOR and CRF receptors (CRF R) may interact in the production of stress-related behaviors but it is not known whether this interaction is involved in reinstatement of alcohol seeking.MethodsMale Long Evans rats were trained to self-administer alcohol (12% w/v). After extinction of responding, we determined the effects of the KOR agonist, U50,488 (2.5, 5 mg/kg) on reinstatement of alcohol seeking, and their sensitivity to the selective KOR antagonist nor-binaltorphimine dihydrochloride (nor-BNI) (10 mg/kg) administered at different times before U50,488. We then examined the effects of nor-BNI on reinstatement induced by the stressor yohimbine (1.25 mg/kg) and on reinstatement induced by exposure to alcohol-associated cues. Finally, we determined whether CRF R1 blockade with antalarmin (10, 20 mg/kg) attenuates alcohol seeking induced by U50,488.ResultsU50,488 reinstated alcohol seeking. Prior treatment with nor-BNI 2, but not 24 h before administration of U50,488 or yohimbine blocked reinstatement induced by these drugs. Cue-induced reinstatement was blocked by nor-BNI administered 2 h prior to testing. Finally, U50,488-induced reinstatement was blocked by antalarmin.ConclusionsThese data further support a role for KOR in reinstatement of alcohol seeking under nonstress and stressful conditions and that KOR and CRF R interact in these effects.

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The CRF1 receptor antagonist antalarmin attenuates yohimbine-induced increases in operant alcohol self-administration and reinstatement of alcohol seeking in rats

Abstract: These results suggest that extrahypothalamic CRF1 receptors are involved in the effect of yohimbine on operant alcohol self-administration and on relapse to alcohol seeking and support the notion that CRF1 receptor antagonists should be considered in alcohol addiction treatment.

Cited by 175 publications

References 90 publications

Mifepristone in the Central Nucleus of the Amygdala Reduces Yohimbine Stress-Induced Reinstatement of Ethanol-Seeking

Mifepristone in the Central Nucleus of the Amygdala Reduces Yohimbine Stress-Induced Reinstatement of Ethanol-Seeking

Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice

The role of kappa opioid receptors in stress‐induced reinstatement of alcohol seeking in rats

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