scholarly journals The Effects of Varenicline on Alcohol Seeking and Self-Administration in Baboons

2013 ◽  
Vol 38 (2) ◽  
pp. 376-383 ◽  
Author(s):  
Barbara J. Kaminski ◽  
Elise M. Weerts

2018 ◽  
Author(s):  
Danai Riga ◽  
Leanne JM Schmitz ◽  
Yvar van Mourik ◽  
Witte JG Hoogendijk ◽  
Taco J De Vries ◽  
...  

AbstractMajor depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat-induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (5 episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction and cue-induced reinstatement of alcohol-seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, excessive motivation to acquire alcohol, persistent alcohol-seeking despite alcohol unavailability, extinction resistance and increased cue-induced relapse; the latter could be blocked by the α2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol-seeking and -taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.



2017 ◽  
Vol 42 (9) ◽  
pp. 1789-1799 ◽  
Author(s):  
Eric Augier ◽  
Russell S Dulman ◽  
Ruslan Damadzic ◽  
Andrew Pilling ◽  
J Paul Hamilton ◽  
...  




2019 ◽  
Author(s):  
Koral Goltseker ◽  
Hen Handrus ◽  
Segev Barak

AbstractRelapse to alcohol abuse is often caused by exposure to potent alcohol-associated cues. Therefore, disruption of the cue-alcohol memory can prevent relapse. It is believed that memories destabilize and become prone for updating upon their reactivation through retrieval, and then re-stabilize within 6 h during a “reconsolidation” process. We recently showed that relapse to cocaine seeking could be prevented by counterconditioning the cocaine-cues with aversive outcomes following cocaine-memory retrieval, in a place conditioning paradigm. However, to better model addiction-related behaviors, self-administration models are necessary. Here, we demonstrate that relapse to alcohol seeking can be prevented by aversive counterconditioning conducted during alcohol-memory reconsolidation, in conditioned place preference (CPP) and operant self-administration paradigms, in mice and rats, respectively. We found that the reinstatement of alcohol-CPP was abolished only when aversive counterconditioning with water-flooding was given shortly after alcohol-memory retrieval. Furthermore, rats trained to lever-press for alcohol showed decreased context-induced renewal of alcohol-seeking responding when the lever-pressing was counterconditioned with foot-shocks, shortly, but not 6 h, after memory retrieval. These results 0suggest that aversive counterconditioning can prevent relapse to alcohol seeking only when performed during alcohol-memory reconsolidation, presumably by updating, or replacing, the alcohol memory with aversive information. Also, we found that aversive counterconditioning preceded by alcohol-memory retrieval was characterized by upregulation of brain-derived neurotrophic factor (Bdnf) mRNA expression in the medial prefrontal cortex, suggesting that Bdnf plays a role in the memory updating process.



2012 ◽  
Vol 227 (1) ◽  
pp. 127-136 ◽  
Author(s):  
Barbara J. Kaminski ◽  
Michael L. Van Linn ◽  
James M. Cook ◽  
Wenyuan Yin ◽  
Elise M. Weerts


2007 ◽  
Vol 12 (1) ◽  
pp. 35-50 ◽  
Author(s):  
Christian A. Heidbreder ◽  
Michela Andreoli ◽  
Cristina Marcon ◽  
Daniel M. Hutcheson ◽  
Eliot L. Gardner ◽  
...  


2021 ◽  
Author(s):  
Melissa A. Cyders ◽  
Martin H. Plawecki ◽  
Zachary T. Whitt ◽  
Ann E.K. Kosobud ◽  
David A. Kareken ◽  
...  


Author(s):  
Paola Maccioni ◽  
Katarzyna Kaczanowska ◽  
Harshani Lawrence ◽  
Sang Yun ◽  
Jessica Bratzu ◽  
...  

Positive allosteric modulators (PAMs) of the GABAB receptor (GABAB PAMs) are of interest in the addiction field due to their ability to suppress several behaviors motivated by drugs of abuse. KK-92A is a novel GABAB PAM found to attenuate intravenous self-administration of nicotine and reinstatement of nicotine seeking in rats. This present study was aimed at extending to alcohol the anti-addictive properties of KK-92A. To this end, Sardinian alcohol-preferring rats were trained to lever-respond for oral alcohol (15% v/v) or sucrose (0.7% w/v) under the fixed ratio (FR) 5 (FR5) schedule of reinforcement. Once lever-responding behavior had stabilized, rats were exposed to tests with acutely administered KK-92A under FR5 and progressive ratio schedules of reinforcement and cue-induced reinstatement of previously extinguished alcohol seeking. KK-92A effect on spontaneous locomotor activity was also evaluated. Treatment with 10 and 20 mg/kg KK-92A suppressed lever-responding for alcohol, amount of self-administered alcohol, and breakpoint for alcohol. Treatment with 20 mg/kg KK-92A reduced sucrose self-administration. Combination of per se ineffective doses of KK-92A (2.5 mg/kg) and the GABAB receptor agonist, baclofen (1 mg/kg), reduced alcohol self-administration. Treatment with 5, 10, and 20 mg/kg KK-92A suppressed reinstatement of alcohol seeking. Only treatment with 80 mg/kg KK-92A affected spontaneous locomotor activity. These results demonstrate the ability of KK-92A to inhibit alcohol-motivated behaviors in rodents and confirm that these effects are common to the entire class of GABAB PAMs. The remarkable efficacy of KK-92A is discussed in terms of its ago-allosteric properties.



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