Background
Synthetic cathinones, 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), serve as a substrate or blocker at monoaminergic transporters, respectively, and produce locomotor stimulant effects in rodents. The present study investigated in rats the effects of repeated exposure to 4-MMC, MDPV, or mixtures of the two on the induction of locomotor sensitization and expression of cross-sensitization to cocaine.
Methods
Seventy-two male Sprague-Dawley rats received daily intraperitoneal injections of saline, MDPV (0.5 mg/kg), 4-MMC (0.5, 1.0, or 2.0 mg/kg) or mixtures of 0.5 mg/kg MDPV + 4-MMC (0.5, 1.0, or 2.0 mg/kg) for seven consecutive days. Locomotor activity was recorded on days 1 and 7 and again after an acute injection of 5 mg/kg cocaine following a 10 day drug washout period.
Results
Rats injected with 0.5 mg/kg MDPV, 0.5, 1.0, or 2.0 mg/kg 4-MMC, or 2.0 mg/kg 4-MMC + 0.5 mg/kg MDPV displayed time-dependent increases in horizontal activity that were augmented on day 7 compared to day 1. In addition, rats pretreated with 0.5 mg/kg MDPV, 2.0 mg/kg 4-MMC, or mixtures of 4-MMC + MDPV displayed an enhanced response to cocaine.
Conclusions
Locomotor responses sensitize to MDPV and to certain mixtures of MDPV and 4-MMC following repeated dosing. Furthermore, previous exposure to these substances may produce cross-sensitization to the locomotor stimulant effects of cocaine. Considered together with recent findings that 4-MMC and MDPV have different sites of action, but both influence monoaminergic functioning, further investigations utilizing a variety of behavioral assays may prove informative regarding the abuse liability of synthetic cathinone mixtures.
Objective: Howard Rachlin wrote extensively on how value diminishes in a hyperbolic form, and he contributed to understanding choice processes between different commodities as a molar pattern of behavior. The field of behavioral economic demand has been dominated by exponential decay functions, indicating that decreases in consumption of a commodity are best fit by exponential functions. Because of the success of Rachlin’s equation at describing how hyperbolic decay affects the value of a commodity across various factors (e.g., delay, probability, social distance), we attempted to extend his equation to behavioral economic demand data for alcohol and opioids. Method: Rachlin’s discounting equation was applied to estimate consumption on alcohol purchase task data and nonhuman drug demand data. We compared results of his equation to the exponentiated demand equation using both a mixed-effects modeling approach and a two-stage approach. Results: Rachlin’s equation provided better fits to consumption data than the exponentiated equation for both mixed-effects and two-stage modeling. We also found that traditional demand metrics, such as Pmax, can be derived analytically when using Rachlin’s equation. Certain metrics derived from Rachlin’s equation appeared to be related to clinical covariates in ways similar to the exponentiated equation. Conclusions: Rachlin’s equation better described demand data than did the exponentiated equation, indicating that demand for a commodity may decrease hyperbolically rather than exponentially. Other benefits of his equation are that it does not have the same pitfalls as the current exponential equations and is relatively straightforward in its conceptualization when applied to demand data.
Contingency management (CM), in which financial incentives are provided upon verification of abstinence from alcohol, cigarettes, and/or illicit substances, is one of the most highly effective and empirically supported treatments for substance use disorders. However, the financial cost of implementation has been identified as a major barrier to implementation of this treatment. The purpose of this study was to develop behavioral economic purchase tasks to assess interest in CM as a function of treatment cost and perceived effectiveness of CM as a function of abstinence incentive size in alcohol drinkers. Alcohol drinkers recruited from Amazon Mechanical Turk (MTurk) completed behavioral economic purchase tasks measuring demand for CM based on targeted abstinence intervals and treatment effectiveness and alcohol use disorder severity assessments. Nonlinear mixed-effects modeling was used to fit demand curves and assess the relationship between individual characteristics and demand metrics for CM. Results reveal that participants reported higher probability of remaining abstinent from drinking when offered larger incentives and required larger incentives when duration of abstinence required to earn the incentive was increased. Additionally, willingness to pay for treatment increased as effectiveness of treatment increased. Abstinence interval and treatment effectiveness are important features to consider when developing effective CM for widespread use, as these variables affected participants’ likelihood of being abstinent and their interest in treatment. Future work will validate these assessments with actual treatment outcomes and determine predictors of CM treatment effectiveness.
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