A dopamine transport inhibitor with markedly low abuse liability suppresses cocaine self-administration in the rat

2009 ◽  
Vol 207 (2) ◽  
pp. 281-289 ◽  
Author(s):  
Antonio Ferragud ◽  
Clara Velázquez-Sánchez ◽  
Vicente Hernández-Rabaza ◽  
Amparo Nácher ◽  
Virginia Merino ◽  
...  
Keyword(s):  
Abuse Liability ◽  
Self Administration ◽  
Transport Inhibitor ◽  
Dopamine Transport

scholarly journals Self-administration of the anandamide transport inhibitor AM404 by squirrel monkeys

2016 ◽  
Vol 233 (10) ◽  
pp. 1867-1877 ◽  
Author(s):  
Charles W. Schindler ◽  
Maria Scherma ◽  
Godfrey H. Redhi ◽  
Subramanian K. Vadivel ◽  
Alexandros Makriyannis ◽  
...  
Keyword(s):  
Squirrel Monkeys ◽  
Self Administration ◽  
Transport Inhibitor ◽  
Anandamide Transport

Evaluation of abuse liability using self-administration, extinction and reinstatement in the monkey using cocaine and fentanyl

2012 ◽  
Vol 66 (2) ◽  
pp. 167
Author(s):  
David A. Hygate ◽  
Rex Manguiat ◽  
Wei Jie Wong ◽  
Sonali Medakkar ◽  
Daniel M. Hutcheson
Keyword(s):  
Abuse Liability ◽  
Self Administration

scholarly journals Effects of Kappa Opioid Receptor Agonists on Fentanyl vs. Food Choice in Male and Female Rats: Contingent vs. Non-Contingent Administration

2020 ◽  
Author(s):  
E. Andrew Townsend
Keyword(s):  
Opioid Receptor ◽  
Food Choice ◽  
Food Reinforcement ◽  
Abuse Liability ◽  
Kappa Opioid Receptor ◽  
Female Rats ◽  
Self Administration ◽  
Kappa Opioid ◽  
Male And Female ◽  
Male And Female Rats

AbstractRationaleStrategies are needed to decrease the abuse liability of mu opioid receptor (MOR) agonists. One strategy under consideration is to combine MOR agonists with kappa opioid receptor (KOR) agonists.ObjectivesThe effects of KOR-agonists (U50488, nalfurafine) on fentanyl-versus-food choice were compared under conditions where the KOR agonists were added to the self-administered fentanyl (contingent delivery) or administered as pretreatments (non-contingent delivery) in male and female rats. The effects of increasing and decreasing the magnitude of the alternative food reinforcer were also determined.MethodsRats were trained to respond under a concurrent schedule of fentanyl (0, 0.32-10 μg/kg/infusion) and food reinforcement. In Experiment 1, U50488 and nalfurafine were co-administered with fentanyl as fixed-proportion mixtures (contingent administration). In Experiment 2, U50488 (1-10 mg/kg) and nalfurafine (3.2-32 μg/kg) were administered as acute pretreatments (non-contingent administration). nor-BNI (32 mg/kg) was administered prior to contingent and non-contingent KOR-agonist treatment in Experiment 3. Experiment 4 evaluated the effects of increasing and decreasing the magnitude of the non-drug reinforcer.ResultsBoth U50488 and nalfurafine decreased fentanyl choice when administered contingently, demonstrating that KOR agonists punish opioid choice. Non-contingent U50488 and nalfurafine administration decreased rates of fentanyl and food self-administration without altering fentanyl choice. Both contingent and non-contingent U50488 and nalfurafine effects on fentanyl choice were attenuated by nor-BNI. Fentanyl choice was sensitive to increases and decreases in the magnitude of the non-drug reinforcer.ConclusionsThese results demonstrate that the effects of KOR agonists on fentanyl reinforcement are dependent upon the contingencies under which they are administered.

scholarly journals Spontaneously Hypertensive Rat substrains show differences in premorbid addiction vulnerability traits and cocaine self-administration: Implications for a novel rat reduced complexity cross

2021 ◽  
Author(s):  
Kathleen M. Kantak ◽  
Carissa Stots ◽  
Elon Mathieson ◽  
Camron D. Bryant
Keyword(s):  
Genetic Mapping ◽  
Complex Traits ◽  
Cocaine Abuse ◽  
Spontaneously Hypertensive Rat ◽  
Abuse Liability ◽  
List Type ◽  
Self Administration ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Reduced Complexity

ABSTRACTForward genetic mapping of F2 crosses between closely related substrains of inbred rodents - referred to as a reduced complexity cross (RCC) - is a relatively new strategy for accelerating the pace of gene discovery for complex traits, such as drug addiction. RCCs to date were generated in mice, but rats are thought to be optimal for addiction genetic studies. Based on past literature, one inbred Spontaneously Hypertensive Rat substrain, SHR/NCrl, is predicted to exhibit a distinct behavioral profile as it relates to cocaine vulnerability traits relative to another substrain, SHR/NHsd. Direct substrain comparisons are a necessary first step before implementing an RCC. We evaluated a number of premorbid addiction vulnerability traits and cocaine self-administration behaviors using a longitudinal within-subjects design. Trait impulsivity and compulsivity were greater in SHR/NCrl than SHR/NHsd, as were reactivity to sucrose reward, sensitivity to acute psychostimulant effects of cocaine, and cocaine abuse liability studied under fixed-ratio and chained schedules of cocaine self-administration. Trait compulsivity correlated with the acute psychostimulant effects of cocaine, which in turn correlated with cocaine taking under the chained schedule. Trait compulsivity also was the best predictor of cocaine seeking responses. Heritability estimates indicated that 22%-40% of the variances for the above phenotypes can be explained by additive genetic factors, providing sufficient genetic variance to conduct genetic mapping in F2 crosses of SHR/NCrl and SHR/NHsd. These results provide compelling support for using an RCC approach in SHR substrains to uncover candidate genes and variants that are of relevance to cocaine use disorders.HighlightsClosely related SHR substrains have distinct cocaine vulnerability traitsInhibitory control was poorer in SHR/NCrl than SHR/NHsdSHR/NCrl were more sucrose reactive and sensitive to acute cocaine than SHR/NHsdCocaine abuse liability was greater in SHR/NCrl than SHR/NHsdSHR substrains can be used in an RCC to uncover cocaine vulnerability genes & variants

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