Effects of access condition on substance use disorder-like phenotypes in male and female rats self-administering MDPV or cocaine.

Substance use disorder (SUD) is a heterogeneous disorder, where severity, symptoms, and patterns of use vary across individuals. Yet, when rats self-administer cocaine under short-access conditions, their behavior tends to be well-regulated, though individual differences can emerge with long- or intermittent-access. In contrast, significant individual differences emerge when rats self-administer 3,4-methylenedioxypyrovalerone (MDPV), even under short-access conditions, wherein ~30 % of rats exhibit high levels of drug-taking.

Impacts of Self-Administered 3,4-Methylenedioxypyrovalerone (MDPV) Alone, and in Combination with Caffeine, on Recognition Memory and Striatal Monoamine Neurochemistry in Male Sprague Dawley Rats: Comparisons with Methamphetamine and Cocaine.

Recent data suggest that 3,4-methylenedioxypyrovalerone (MDPV) has neurotoxic effects; however, the cognitive and neurochemical consequences of MDPV self-administration remain largely unexplored. Furthermore, despite the fact that drug preparations that contain MDPV often also contain caffeine, little is known regarding the toxic effects produced by the co-use of these two stimulants. The current study investigated the degree to which self-administered MDPV or a mixture of MDPV+caffeine can produce deficits in recognition memory and alter neurochemistry relative to prototypical stimulants.

Effects of access condition on substance use disorder-like phenotypes in male and female rats self-administering MDPV or cocaine.

Substance use disorder (SUD) is a heterogeneous disorder, where severity, symptoms, and patterns of substance use vary across individuals. Yet, when rats are allowed to self-administer drugs such as cocaine under short-access conditions, their behavior tends to be well-regulated and homogeneous in nature; though individual differences can emerge when rats are provided long- or intermittent-access to cocaine. In contrast to cocaine, significant individual differences emerge when rats are allowed to self-administer 3,4-methylenedioxypyrovalerone (MDPV), even under short-access conditions, wherein ~30% of rats rapidly transition to high levels of drug-taking.

Impacts of Self-Administered 3,4-Methylenedioxypyrovalerone (MDPV) Alone, and in Combination with Caffeine, on Recognition Memory and Striatal Monoamine Neurochemistry in Male Sprague-Dawley Rats: Comparisons with Methamphetamine and Cocaine.

Recent data suggest that 3,4-methylenedioxypyrovalerone (MDPV) has neurotoxic effects; however, the cognitive and neurochemical consequences of MDPV self-administration remain largely unexplored. Furthermore, despite the fact that drug preparations that contain MDPV often also contain caffeine, little is known regarding the toxic effects produced by the co-use of these two stimulants. The current study investigated the degree to which self-administered MDPV, or a mixture of MDPV+caffeine can produce deficits in recognition memory and alter neurochemistry relative to prototypical stimulants.

Cardiovascular and Locomotor Effects of Binary Mixtures of Common "Bath Salts" Constituents: Studies with Methylone, MDPV, and Caffeine in Rats.

Background And Purpose: The use of "Bath Salts" drug preparations has been associated with high rates of toxicity and death. Preparations often contain mixtures of drugs including multiple synthetic cathinones or synthetic cathinones and caffeine; however, little is known about whether interactions among "Bath Salts" constituents contribute to the adverse effects often reported in users.

Experimental Approach: This study used adult male Sprague-Dawley rats to characterize the cardiovascular effects, locomotor effects, and pharmacokinetics of methylone, MDPV, and caffeine, administered alone and as binary mixtures.

3,4-Methylenedioxypyrovalerone High-Responder Phenotype as a Tool to Evaluate Candidate Medications for Stimulant Use Disorder.

Despite decades of research, there are no medications approved by the United States Food and Drug Administration to treat stimulant use disorders. Self-administration procedures are widely used to screen candidate medications for stimulant use disorder, although preclinical reductions in stimulant self-administration have not translated to meaningful reductions in stimulant use in humans. One possible reason for this discordance is that most preclinical studies evaluate candidate medications under conditions that promote predictable, and well-regulated patterns of drug-taking rather than the dysregulated and/or compulsive patterns of drug-taking characteristic of a stimulant use disorder.

Interactions between impulsivity and MDPV self-administration in rats.

Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone (MDPV), are recreational drugs of abuse often identified in 'bath salts' preparations. Humans report compulsive patterns of bath salts use, and previous work suggests that a subset of rats develop unusually high levels of MDPV self-administration. This study aims to test the hypothesis that high levels of impulsivity (e.

Modeling Stimulant and Opioid Co-use in Rats Provided Concurrent Access to Methamphetamine and Fentanyl.

Concurrent use of stimulants (e.g., methamphetamine) and opioids (e.

Application of dose-addition analyses to characterize the abuse-related effects of drug mixtures.

Polysubstance use makes up a majority of drug use, yet relatively few studies investigate the abuse-related effects of drug mixtures. Dose-addition analyses provide a rigorous and quantitative method to determine the nature of the interaction (i.e.

Relative reinforcing effects of cocaine and 3,4-methylenedioxypyrovalerone (MDPV) under a concurrent access self-administration procedure in rats.

Background: Recent evidence suggesting that polysubstance use is the norm rather than the exception highlights the need for a better understanding of interactions amongst the abuse-related effects of commonly co-abused drugs. Synthetic cathinones remain one of the most popular families of novel psychoactive substances and are typically used in preparations containing multiple stimulants. Evaluating the reinforcing effects of drugs under both single-operant procedures and procedures in which alternatives are available can provide a more complete characterization of their reinforcing effects and economic interactions.

Influence of Contingent and Noncontingent Drug Histories on the Development of High Levels of MDPV Self-Administration.

A subset of rats that self-administer 3,4-methylenedioxypyrovalerone (MDPV) develop unusually high levels of drug taking. A history of responding maintained by cocaine, but not food, prevents the development of this high-responder phenotype; however, it is unclear how histories of noncontingent cocaine exposure or self-administering drugs from other pharmacological classes would affect its development. In the current studies, 5 groups of male Sprague-Dawley rats were used to determine whether histories of responding maintained by drugs from different pharmacological classes (e.

Impact of Morphine Dependence and Withdrawal on the Reinforcing Effectiveness of Fentanyl, Cocaine, and Methamphetamine in Rats.

Recent estimates suggest increased popularity of the concurrent use of opioids and stimulants, with over 50% of treatment-seeking opioid users reporting regular stimulant use. The goal of the current study was to determine how opioid dependence and withdrawal affect the reinforcing effects of fentanyl, cocaine, and methamphetamine. Male Sprague-Dawley rats were allowed to self-administer fentanyl under a progressive ratio (PR) schedule of reinforcement.

Discriminative stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) and structurally related synthetic cathinones.

The 3,4-methylenedioxypyrovalerone (MDPV), and other structurally related synthetic cathinones, are popular alternatives to prototypical illicit psychostimulants, such as cocaine and methamphetamine. These drugs are often referred to as 'bath salts' and function either as cocaine-like inhibitors of monoamine uptake, or amphetamine-like substrates for dopamine, norepinephrine and serotonin transporters. These studies used male Sprague-Dawley rats trained to discriminate MDPV from saline to evaluate the substitution profiles of structurally related synthetic cathinones, cocaine, and other direct-acting dopamine and noradrenergic receptor agonists in order to characterize the relative contributions of dopamine, norepinephrine and serotonin to the discriminative stimulus effects of MDPV.

MDPV self-administration in female rats: influence of reinforcement history.

Rationale: A subset of male rats that self-administer 3,4-methylenedioxypyrovalerone (MDPV) have unusually high levels of drug intake; however, factor(s) that influence this behavior (e.g., reinforcement history and sex) are unknown.

Interactions between reinforcement history and drug-primed reinstatement: Studies with MDPV and mixtures of MDPV and caffeine.

Many drugs of abuse are mixed with other psychoactive substances (e.g., caffeine) prior to their sale or use.

Self-administration of the synthetic cathinones 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopentiophenone (α-PVP) in rhesus monkeys.

Rationale: The availability and abuse of synthetic analogues of cathinone have increased dramatically around the world. Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone [MDPV] and α-pyrrolidinopentiophenone [α-PVP], are cocaine-like inhibitors of monoamine transporters and common constituents of "bath salts" or "flakka" preparations. Studies in rats suggest that MDPV and α-PVP are 3 to 4-fold more effective reinforcers than cocaine; however, comparisons of the relative reinforcing effectiveness of MDPV and α-PVP have not been reported in other species.

Effects of lorcaserin on reinstatement of responding previously maintained by cocaine or remifentanil in rhesus monkeys.

Drug abuse remains a serious public health issue, underscoring the need for additional treatment options. Agonists at serotonin (5-HT)2C receptors, particularly lorcaserin, are being considered as pharmacotherapies for abuse of a variety of drugs, including cocaine and opioids. The current study compared the capacity of lorcaserin to attenuate reinstatement of extinguished responding previously maintained by either cocaine or an opioid; this type of procedure is thought to model relapse, an important aspect of drug abuse.

The abuse-related effects of pyrrolidine-containing cathinones are related to their potency and selectivity to inhibit the dopamine transporter.

Synthetic cathinones are common constituents of abused "bath salts" preparations and represent a large family of structurally related compounds that function as cocaine-like inhibitors or amphetamine-like substrates of dopamine (DAT), norepinephrine (NET), and serotonin (SERT) transporters. Preclinical evidence suggests that some cathinones (e.g.

Behavioral economic analysis of the reinforcing effects of "bath salts" mixtures: studies with MDPV, methylone, and caffeine in male Sprague-Dawley rats.

Rationale: "Bath salts" preparations often contain combinations of synthetic cathinones (e.g., 3,4-methylenedioxymethcathinone [methylone], 3,4-methylenedioxypyrovalerone [MDPV]), and caffeine, and evidence suggests that mixtures of synthetic cathinones and caffeine (e.

Effects of lorcaserin and buspirone, administered alone and as a mixture, on cocaine self-administration in male and female rhesus monkeys.

Cocaine use disorder is a serious public health issue for which there is no effective pharmacotherapy. One strategy to speed development of medications for cocaine use disorder is to repurpose drugs already approved for use in humans based on their ability to interact with targets known to be important for addiction. Two such drugs, lorcaserin (Belviq; a drug with serotonin [5-HT]2C receptor agonist properties) and buspirone (Buspar; a drug with 5-HT1A receptor partial agonist and dopamine D3/D4 receptor antagonist properties) can produce modest decreases in cocaine self-administration in rhesus monkeys.

The behavioral pharmacology and therapeutic potential of lorcaserin for substance use disorders.

Substance abuse is serious public health problem for which there are few effective pharmacotherapies. Traditional strategies for drug development have focused on antagonists to block the abuse-related effects of a drug at its site of action, and agonists to replace/mimic the effects of the abused substance. However, recent efforts have targeted receptors, such as serotonin (5-HT) receptors, that can indirectly modulate dopamine neurotransmission with the goal of developing a pharmacotherapy that might be effective at reducing the abuse-related effects of drugs more generally.

Relative reinforcing effects of second-generation synthetic cathinones: Acquisition of self-administration and fixed ratio dose-response curves in rats.

"Bath salts" preparations contain synthetic cathinones which interact with monoamine transporters and function as either monoamine uptake inhibitors or releasers. 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxymethcathinone (methylone), and 4-methylmethcathinone (mephedrone) were three of the most common cathinones (i.e.

Reinforcing Effects of Binary Mixtures of Common Bath Salt Constituents: Studies with 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-Methylenedioxymethcathinone (methylone), and Caffeine in Rats.

Bath salts use is associated with high rates of abuse, toxicity, and death. Bath salt preparations often contain mixtures of drugs including multiple synthetic cathinones (eg, 3,4-methylenedioxypyrovalerone (MDPV) or 3,4-methylenedioxymethcathinone (methylone)) or synthetic cathinones and caffeine; however, little is known about whether interactions among bath salt constituents contribute to the abuse-related effects of bath salts preparations. This study used male Sprague-Dawley rats responding under a progressive ratio schedule to quantify the reinforcing effectiveness of MDPV, methylone, and caffeine, administered alone and as binary mixtures (n=12 per mixture).

Reinforcing effects of abused 'bath salts' constituents 3,4-methylenedioxypyrovalerone and α-pyrrolidinopentiophenone and their enantiomers.

Synthetic cathinones found in abused 'bath salts' preparations are chiral molecules. Racemic 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopentiophenone (α-PVP) are two common constituents of these preparations that have been reported to be highly effective reinforcers; however, the relative contribution of each enantiomer toward these effects has not been determined. Thus, male Sprague-Dawley rats were trained to respond for racemic MDPV or α-PVP (n=9/drug), with full dose-response curves for the racemate and the S and R enantiomers of MDPV and α-PVP generated under a progressive ratio schedule of reinforcement.