scholarly journals The Antagonism of Corticotropin-Releasing Factor Receptor-1 in Brain Suppress Stress-Induced Propofol Self-Administration in Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Zhanglei Dong ◽  
Gaolong Zhang ◽  
Saiqiong Xiang ◽  
Chenchen Jiang ◽  
Zhichuan Chen ◽  
...  
Keyword(s):  
Behavioral Model ◽  
Treated Group ◽  
Reward Processing ◽  
D1 Receptor ◽  
Corticotropin Releasing Factor ◽  
Self Administration ◽  
Candidate Target ◽  
Stressful Stimulation ◽  
Locomotor Activities ◽  
Tail Clip

Propofol addiction has been detected in humans and rats, which may be facilitated by stress. Corticotropin-releasing factor acts through the corticotropin-releasing factor (CRF) receptor-1 (CRF1R) and CRF2 receptor-2 (CRF2R) and is a crucial candidate target for the interaction between stress and drug abuse, but its role on propofol addiction remains unknown. Tail clip stressful stimulation was performed in rats to test the stress on the establishment of the propofol self-administration behavioral model. Thereafter, the rats were pretreated before the testing session at the bilateral lateral ventricle with one of the doses of antalarmin (CRF1R antagonist, 100–500 ng/site), antisauvagine 30 (CRF2R antagonist, 100–500 ng/site), and RU486 (glucocorticoid receptor antagonist, 100–500 ng/site) or vehicle. The dopamine D1 receptor (D1R) in the nucleus accumbens (NAc) was detected to explore the underlying molecular mechanism. The sucrose self-administration establishment and maintenance, and locomotor activities were also examined to determine the specificity. We found that the establishment of propofol self-administration was promoted in the tail clip treated group (the stress group), which was inhibited by antalarmin at the dose of 100–500 ng/site but was not by antisauvagine 30 or RU486. Accordingly, the expression of D1R in the NAc was attenuated by antalarmin, dose-dependently. Moreover, pretreatments fail to change sucrose self-administration behavior or locomotor activities. This study supports the role of CRF1R in the brain in mediating the central reward processing through D1R in the NAc and provided a possibility that CRF1R antagonist may be a new therapeutic approach for the treatment of propofol addiction.

A Critical Evaluation of a Nicotine Vaccine within a Self-Administration Behavioral Model

2010 ◽  
Vol 7 (2) ◽  
pp. 431-441 ◽  
Author(s):  
Amira Y. Moreno ◽  
Marc R. Azar ◽  
Noelle A. Warren ◽  
Tobin J. Dickerson ◽  
George F. Koob ◽  
...  
Keyword(s):  
Critical Evaluation ◽  
Behavioral Model ◽  
Self Administration

scholarly journals Extended access cocaine self-administration differentially activates dorsal raphe and amygdala corticotropin-releasing factor systems in rats

2011 ◽  
Vol 17 (2) ◽  
pp. 300-308 ◽  
Author(s):  
Eric P. Zorrilla ◽  
Sunmee Wee ◽  
Yu Zhao ◽  
Sheila Specio ◽  
Benjamin Boutrel ◽  
...  
Keyword(s):  
Dorsal Raphe ◽  
Corticotropin Releasing Factor ◽  
Self Administration ◽  
Extended Access ◽  
Dorsal Raphé

scholarly journals A Neurofunctional Domains Approach to Evaluate D1/D5 Dopamine Receptor Partial Agonism on Cognition and Motivation in Healthy Volunteers With Low Working Memory Capacity

2020 ◽  
Vol 23 (5) ◽  
pp. 287-299
Author(s):  
Rita Balice-Gordon ◽  
Garry D Honey ◽  
Christopher Chatham ◽  
Estibaliz Arce ◽  
Sridhar Duvvuri ◽  
...  
Keyword(s):  
Working Memory ◽  
Adverse Events ◽  
Partial Agonist ◽  
Working Memory Capacity ◽  
Dose Range ◽  
Specific Treatment ◽  
Memory Capacity ◽  
Dopamine D1 Receptor ◽  
Reward Processing ◽  
D1 Receptor

Abstract Background Dopamine D1 receptor signaling plays key roles in core domains of neural function, including cognition and reward processing; however, many questions remain about the functions of circuits modulated by dopamine D1 receptor, largely because clinically viable, selective agonists have yet to be tested in humans. Methods Using a novel, exploratory neurofunctional domains study design, we assessed the safety, tolerability, pharmacodynamics, and pharmacokinetics of PF-06412562, a selective D1/D5R partial agonist, in healthy male volunteers who met prespecified criteria for low working memory capacity. Functional magnetic resonance imaging, electrophysiologic endpoints, and behavioral paradigms were used to assess working memory, executive function, and motivation/reward processing following multiple-dose administration of PF-06412562. A total of 77 patients were assigned PF-06412562 (3 mg twice daily and 15 mg twice daily) or placebo administered for 5 to 7 days. Due to the exploratory nature of the study, it was neither powered for any specific treatment effect nor corrected for multiple comparisons. Results Nominally significant improvements from baseline in cognitive endpoints were observed in all 3 groups; however, improvements in PF-06412562–treated patients were less than in placebo-treated participants. Motivation/reward processing endpoints were variable. PF-06412562 was safe and well tolerated, with no serious adverse events, severe adverse events, or adverse events leading to dose reduction or temporary discontinuation except for 1 permanent discontinuation due to increased orthostatic heart rate. Conclusions PF-06412562, in the dose range and patient population explored in this study, did not improve cognitive function or motivation/reward processing more than placebo over the 5- to 7-day treatment period. ClinicalTrials.gov Identifier NCT02306876

scholarly journals Corticotropin-Releasing Factor 1 Antagonists Selectively Reduce Ethanol Self-Administration in Ethanol-Dependent Rats

2007 ◽  
Vol 61 (1) ◽  
pp. 78-86 ◽  
Author(s):  
Cindy K. Funk ◽  
Eric P. Zorrilla ◽  
Mei-Jing Lee ◽  
Kenner C. Rice ◽  
George F. Koob
Keyword(s):  
Corticotropin Releasing Factor ◽  
Self Administration
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