scholarly journals Predicting the Abuse Liability of Entactogen-Class, New and Emerging Psychoactive Substances via Preclinical Models of Drug Self-administration

2016 ◽  
pp. 145-164 ◽  
Author(s):  
Shawn M. Aarde ◽  
Michael A. Taffe
Keyword(s):  
Abuse Liability ◽  
Psychoactive Substances ◽  
Preclinical Models ◽  
Self Administration

scholarly journals Abuse of Prescription Drugs in the Context of Novel Psychoactive Substances (NPS): A Systematic Review

2018 ◽  
Vol 8 (4) ◽  
pp. 73 ◽  
Author(s):  
Fabrizio Schifano ◽  
Stefania Chiappini ◽  
John Corkery ◽  
Amira Guirguis
Keyword(s):  
Systematic Review ◽  
Prescription Drugs ◽  
Immediate Release ◽  
Abuse Liability ◽  
Novel Psychoactive Substances ◽  
Psychoactive Substances ◽  
Self Administration ◽  
Second Generation Antipsychotics ◽  
And Performance ◽  
Performance Enhancing Drugs

Recently, a range of prescription and over-the-counter drugs have been reportedly used as Novel Psychoactive Substances (NPS), due to their potential for abuse resulting from their high dosage/idiosyncratic methods of self-administration. This paper provides a systematic review of the topic, focusing on a range of medications which have emerged as being used recreationally, either on their own or in combination with NPS. Among gabapentinoids, pregabalin may present with higher addictive liability levels than gabapentin, with pregabalin being mostly identified in the context of opioid, polydrug intake. For antidepressants, their dopaminergic, stimulant-like, bupropion activities may explain their recreational value and diversion from the therapeutic intended use. In some vulnerable clients, a high dosage of venlafaxine (‘baby ecstasy’) is ingested for recreational purposes, whilst the occurrence of a clinically-relevant withdrawal syndrome may be a significant issue for all venlafaxine-treated patients. Considering second generation antipsychotics, olanzapine appears to be ingested at very large dosages as an ‘ideal trip terminator’, whilst the immediate-release quetiapine formulation may possess proper abuse liability levels. Within the image- and performance- enhancing drugs (IPEDs) group, the beta-2 agonist clenbuterol (‘size zero pill’) is reported to be self-administered for aggressive slimming purposes. Finally, high/very high dosage ingestion of the antidiarrhoeal loperamide has shown recent increasing levels of popularity due to its central recreational, anti-withdrawal, opiatergic effects. The emerging abuse of prescription drugs within the context of a rapidly modifying drug scenario represents a challenge for psychiatry, public health and drug-control policies.

scholarly journals Use of Tramadol for Management of Opioid Use Disorders: Rationale and Recommendations

2018 ◽  
Vol 09 (03) ◽  
pp. 397-403 ◽  
Author(s):  
Yatan Pal Singh Balhara ◽  
Arpit Parmar ◽  
Siddharth Sarkar
Keyword(s):  
Substance Use ◽  
Abuse Liability ◽  
Evidence Based ◽  
Psychoactive Substances ◽  
Opioid Use ◽  
Treatment Services ◽  
Wide Availability ◽  
Current Article ◽  
Disorder Treatment ◽  
Opioid Use Disorders

ABSTRACTOpioids are one of the most common illicit psychoactive substances being used in India. In fact, opioid use disorders are the most common disorder presenting to the substance use disorder treatment centers across the country. Effective and evidence-based interventions are available for management of opioid use disorders. However, the treatment for opioid use disorders remains difficult to access for most of those in need in India. The current article presents the literature on the use of tramadol for the management of opioid use disorders. It also makes recommendations on the use of tramadol for the management of opioid use disorders. Tramadol offers a viable alternative to the existing options for the management of opioid use disorders. It has been found effective when used for this indication. It offers certain major advantages such as easy and wide availability and low abuse liability. It offers a good option to expand the treatment services for opioid use disorders across the country.

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 Establishing Preclinical Withdrawal Syndrome Symptomatology Following Heroin Self-Administration in Male and Female Rats

2020 ◽  
Author(s):  
Cassandra D. Gipson ◽  
Kelly E. Dunn ◽  
Amanda Bull ◽  
Hanaa Ulangkaya ◽  
Aronee Hossain
Keyword(s):  
Phase 1 ◽  
Opioid Withdrawal ◽  
Female Rats ◽  
Preclinical Models ◽  
Self Administration ◽  
Male And Female ◽  
Somatic Signs ◽  
Male And Female Rats ◽  
Opioid Administration ◽  
Abrupt Discontinuation

AbstractOpioid use disorder (OUD) is a significant health problem, and understanding mechanisms of various aspects of OUD including drug use and withdrawal is important. Preclinical models provide an ideal opportunity to evaluate mechanisms underlying opioid withdrawal. Current models are limited by their reliance upon forced opioid administration, focus on the acute (and not protracted) syndrome, and exclusion of females. In this study, male and female rats self-administered heroin (maintenance dose of 12.5 μg/kg/infusion) opioid withdrawal following abrupt discontinuation was measured. In Phase 1, acute withdrawal symptoms were rated in male and female rats at 0, 16, 48, and 72 hrs following the last self-administration session. Total somatic signs increased until 48 hrs (predominantly in females), and heroin intake positively correlated with total somatic signs at the 48 and 72 hr timepoints. Measures of hyperactivity and anxiety-like behavior increased by 16 and 48 hrs, respectively. In Phase 2, symptoms were assessed at baseline, acute, and protracted (168 and 312 hrs after self-administration) timepoints in a subset of male and female rats from Phase 1. The total number of somatic signs did not differ across timepoints, though females displayed significantly higher body temperature at all timepoints compared to males, indicating sex-specific protracted withdrawal symptomatology. These data provide a thorough characterization of rodent opioid withdrawal symptomatology following self-administration and abrupt discontinuation that serve as a foundation for future studies designed to mimic the human experience, and demonstrate the importance of characterizing acute and protracted withdrawal with sex-specificity in preclinical models of opioid self-administration.

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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