A comparison of economic demand and conditioned-cued reinstatement of methamphetamine-seeking or food-seeking in rats

Galuska, Chad M.; Banna, Kelly M.; Willse, Lena Vaughn; Yahyavi-Firouz-Abadi, Noushin; See, Ronald E.

doi:10.1097/fbp.0b013e3283473be4

Cited by 24 publications

(39 citation statements)

References 40 publications

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“…We compared results of the within-session BE paradigm in males and females with results from a conventional (multi-day) BE paradigm in which rats were stabilized at each FR value for multiple days (31). Following training on the conventional BE paradigm, rats were stabilized on the within-session paradigm.…”

Section: Resultsmentioning

confidence: 99%

“…These analyses allow for direct comparison of the same BE variables across species or reinforcers (26, 27). Importantly, the variables measured with this translational approach (particularly α-demand elasticity, and Q 0 – free consumption) have been shown to predict addiction behaviors in both humans (28–30) and animals (16, 25, 31, 32), and may be an effective approach for developing and testing potential pharmacotherapies (16). …”

Section: Introductionmentioning

confidence: 99%

“…Previous methods to generate demand curves required subjects to stabilize responding at multiple different prices (numbers of lever presses per reward) over weeks of testing (31, 33), limiting the ability to assess underlying brain mechanisms or possible pharmacotherapies. This limitation has recently been overcome with the design of a within-session BE procedure for cocaine self-administration (25, 34, 35).…”

Section: Introductionmentioning

confidence: 99%

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Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand

Cox

Bentzley

Regen-Tuero

et al. 2017

Biological Psychiatry

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Background Evidence indicates that oxytocin, an endogenous peptide well known for its role in social behaviors, childbirth and lactation, is a promising addiction pharmacotherapy. We employed a within-session behavioral-economic (BE) procedure in rats to examine oxytocin as a pharmacotherapy for methamphetamine (meth) addiction. The BE paradigm was modeled after BE procedures used to assess motivation for drugs in human addicts. Importantly, the same BE variables assessed across species have been shown to predict later relapse behavior. Thus, the translational potential of preclinical BE studies is particularly strong. Methods We tested the effects of systemic and microinfused oxytocin on demand for self-administered i.v. meth and reinstatement of extinguished meth-seeking in male and female rats using a behavioral economics paradigm. Correlations between meth demand and meth seeking were assessed. Results Females showed greater demand (i.e., motivation) for meth compared to males. In both males and females, meth demand predicted reinstatement of meth-seeking, and systemic oxytocin decreased demand for meth and attenuated reinstatement to meth seeking. Oxytocin was most effective at decreasing meth demand and seeking in rats with the strongest motivation for drug. Finally, we found that these effects of systemic oxytocin were mediated by actions in the nucleus accumbens (NAc). Discussion Oxytocin decreases meth demand and seeking in both sexes, and these effects depend on oxytocin signaling in the NAc. Overall, these data indicate that development of oxytocin-based therapies may be a promising treatment approach for meth addiction in humans.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand

Cox

Bentzley

Regen-Tuero

et al. 2017

Biological Psychiatry

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“…This report extends behavioral-economic theory (7) by establishing a strong, predictive association between economic demand and addiction-like behavior. Previous reports have found that essential value (α) predicts cue-induced reinstatement of methamphetamine seeking (40), and that long-access self-administration of cocaine increases Q 0 while decreasing α (33). Our studies replicate these findings, and significantly extend them by also showing that essential value (α) predicts cocaine-primed reinstatement, drug seeking during abstinence, and compulsive (punished) drug taking.…”

Section: Discussionmentioning

confidence: 99%

Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat

Bentzley

Jhou

Aston‐Jones

2014

Proc. Natl. Acad. Sci. U.S.A.

150

208

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Development of new treatments for drug addiction will depend on high-throughput screening in animal models. However, an addiction biomarker fit for rapid testing, and useful in both humans and animals, is not currently available. Economic models are promising candidates. They offer a structured quantitative approach to modeling behavior that is mathematically identical across species, and accruing evidence indicates economic-based descriptors of human behavior may be particularly useful biomarkers of addiction severity. However, economic demand has not yet been established as a biomarker of addiction-like behavior in animals, an essential final step in linking animal and human studies of addiction through economic models. We recently developed a mathematical approach for rapidly modeling economic demand in rats trained to self-administer cocaine. We show here that economic demand, as both a spontaneous trait and induced state, predicts addiction-like behavior, including relapse propensity, drug seeking in abstinence, and compulsive (punished) drug taking. These findings confirm economic demand as a biomarker of addiction-like behavior in rats. They also support the view that excessive motivation plays an important role in addiction while extending the idea that drug dependence represents a shift from initially recreational to compulsive drug use. Finally, we found that economic demand for cocaine predicted the efficacy of a promising pharmacotherapy (oxytocin) in attenuating cocaineseeking behaviors across individuals, demonstrating that economic measures may be used to rapidly identify the clinical utility of prospective addiction treatments.behavioral economics | reinstatement | extinction | long access | punished responding T here are currently no approved pharmacotherapies for the treatment of cocaine addiction, and timely development of future treatments will depend on animal models that predict the efficacy of treatment in human addicts. This requires a biomarker of addiction suitable for rapid testing in animals, and applicable in humans. However, animal models of neuropsychiatric diseases generally lack predictive validity (1, 2), and prevalent approaches that use drug self-administration in animals have not yet led to a successful clinical treatment for psychostimulant dependence (3, 4).Economic models provide more promising approaches for this needed cross-species addiction biomarker (5, 6). They offer a structured quantitative method to model behavior that is mathematically identical across species (7-9), and accruing evidence indicates economic-based descriptors of human behavior may be particularly useful biomarkers of addiction severity (10)(11)(12)(13)(14). Notably, economic demand has been shown to correlate with lifetime years of cocaine, heroin, marijuana, and benzodiazepine use (15); severity of alcohol dependence (10,11,14) and craving (16); as well as severity of nicotine dependence (12, 13) and craving (17). However, economic demand has not yet been established as a biomarker of addictionli...

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“…A number of studies investigating drug reinforcers have used Hursh and Silberberg's (2008) exponential demand model to quantify reinforcer value (e.g., Bentzley et al, 2013; Galuska et al, 2011; Koffanus & Woods, 2013). This model provides a single number – α – that quantifies the essential value of a reinforcer.…”

Section: Introductionmentioning

confidence: 99%

Dose and elasticity of demand for self-administered cocaine in rats

Kearns

Silberberg²

2016

Behavioural Pharmacology

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The present experiment tested whether the elasticity of demand for self-administered cocaine in rats is dose-dependent. Subjects lever pressed for three different doses of intravenous cocaine – 0.11, 0.33, and 1.0 mg/kg/infusion – on a demand procedure where the number of lever presses required per infusion increased within a session. The main finding was that demand for the 0.11 mg/kg dose was more elastic than it was for the two larger doses. There was no difference in demand elasticity between the 0.33 and 1.0 mg/kg doses. These results parallel findings previously reported in monkeys. The present study also demonstrated that a within-session procedure can be used to generate reliable demand curves.

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A comparison of economic demand and conditioned-cued reinstatement of methamphetamine-seeking or food-seeking in rats

Cited by 24 publications

References 40 publications

Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand

Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand

Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat

Dose and elasticity of demand for self-administered cocaine in rats

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