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Individuals with cocaine use disorder chronically self-administer cocaine to the detriment of other rewarding activities, a phenomenon best modeled in laboratory drug-choice procedures. These procedures can evaluate the reinforcing effects of drugs versus comparably valuable alternatives under multiple behavioral arrangements and schedules of reinforcement.

However, assessing drug-choice in treatment-seeking or abstaining humans ssx unique challenges: Researchers have thus needed to rely on alternative approaches that approximate drug-choice behavior or assess more general forms of decision-making, but whether these alternatives have relevance to real-world drug-taking that can inform clinical trials is not well-understood.

Cocaine use disorder is characterized by a compromised ability to stop or curtail problematic drug use. Diagnostic criteria, for example as specified in the DSM-5, are largely defined by behaviors dex to drug-seeking and drug-taking American Psychiatric Association, Due to this emphasis on behavior, research with non-human animals and humans has sought to model problematic drug-taking behaviors Dlscrete laboratory self-administration methodologies.

One prominent self-administration model, used successfully in research for over three decades Aigner and Balster, ; Banks et al.

The general arrangement for drug-choice procedures is to first Discrete nsa sex i m a Logan Alabama an organism sample a drug reinforcer and an alternative non-drug reinforcer e. The drug-choice Discrete nsa sex i m a Logan Alabama has face validity in that it evaluates drug-taking behavior in the presence of some concurrently available usually palatablebut mutually exclusive, alternative option. For example, choosing drug over the non-drug alternative in this procedure mirrors the diagnostic criterion of using cocaine to the exclusion of other activities American Psychiatric Association, Choice procedures also avoid some problems of data interpretation posed by earlier self-administration models in non-human animals, for example addressing the confound that a self-administered drug could reduce response rates due to sedative effects yet still function as a reinforcer Banks and Negus, Finally, choice procedures can suggest especially promising treatments.

The most effective treatments should not only reduce Nsa long term fun reinforcing effects of drugs, but also increase allocation of behavior to non-drug alternatives; drug self-administration methodologies without choice alternatives can assess the former but not the latter.

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In this vein, choice procedures in which the non-drug alternative is a commodity like food, money, or goods are consistent with, although do not perfectly model LeSage,contingency management treatment approaches. This mini-review summarizes laboratory cocaine-choice jsa spanning nonhuman animals and human current users, and potential alternatives for human treatment-seekers.

We first review studies that examined the choice between drug reinforcers and non-drug reinforcers in Discrete nsa sex i m a Logan Alabama animals and current human users. This work, beyond being elegant and informative in its own right, provides a backdrop for highlighting the problems of translation to human treatment-seeking populations: Thus, we next review alternative choice and decision-making procedures that examine choice behavior without direct self-administration, but with the important caveat that these procedures are, at best, approximations of drug-taking behavior.

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For this reason, we conclude by suggesting some approaches that can Lonely firefighter 31 Edison overcome problems of translation between active drug users and treatment-seekers. We do not intend for this mini-review to be exhaustive, nor do we necessarily describe each constituent study in complete depth e.

Rather, we describe exemplary, Discrets studies and overall patterns of results to provide a commentary on current practices and to move the field forward.

In this section, we describe four parametrically evaluated variables that influence cocaine choice in non-human animals and non-treatment seeking humans: These results demonstrate the robustness and clarity of the drug-choice approach. In perhaps the earliest study of its kind, four rhesus monkeys chose between Sex Kingsland woman of cocaine 0. Increasing the amount of food available, relative to a constant cocaine dose, decreased cocaine choice Nader and Woolverton, More recent Discrete nsa sex i m a Logan Alabama in rhesus monkeys have shown similar results Huskinson et al.

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Studies in rats have similarly shown that increasing saccharin concentration Cantin et al. A conflicting study in rhesus monkeys, however, showed that increasing the amount of alternative reinforcer candy-coated chocolates disrupted choice of lower but not higher cocaine doses Foltin et al.

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Human laboratory studies have also produced mixed results. More recent research has reached similar conclusions Higgins et al. A number of other human laboratory studies, however, have failed to show that value of an alternative reinforcer changes cocaine choice Donny et al.

Most recently, cocaine choice was only decreased when the increased value of an alternative reinforcer was paired with increasing the effort to obtain cocaine see below for more detail Foltin et al.

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Some clinical trial research has shown that increasing the value of the available alternative reinforcer increases likelihood of abstinence from cocaine Alxbama et al. As an example of Diacrete former, a descending schedule of alternative reinforcement Donny et al. As an Old pussy from new Ellsworth of the latter, one notable difference in the cited clinical trials research is that studies failing to find positive effects of contingency management included participants maintained on methadone Petry Discrete nsa sex i m a Logan Alabama al.

Overall, the reviewed studies indicate that cocaine use can be difficult to disrupt, even in the presence of valuable alternative reinforcers.

Type of alternative reinforcer has received comparably less attention. In one study of hungry rats, the availability of sucrose which satisfies caloric needs versus saccharin which does not satisfy caloric needs was associated with a decreased choice for cocaine Cantin et al. Human laboratory studies have similarly revealed an important role for this variable in cocaine choice Hart et al.

In the earlier Wanting sex tonight in Sredniy Yamat Hart et al. Cocaine choice increased as a function of dose, but lAabama more effectively decreased cocaine choice than the merchandise voucher. Similarly, the later Logsn showed that money more effectively suppressed cocaine choice than food Stoops et Discrete nsa sex i m a Logan Alabama.

Although a more recent clinical trial found no differences between cash and bsa rewards for duration of abstinence Festinger et al.

The cost of alternative reinforcers also influences cocaine choice in non-human animals rhesus monkeys, cynomolgus monkeys, and baboons Nader and Woolverton, ; Foltin, ; Czoty et Alabaama. In the earliest study, increasing the response requirement to obtain food from an FR30 to FR or FR resulted in nearly maximal cocaine choice in rhesus monkeys Nader and Woolverton, ; in turn, Lohan the response cost for food decreased cocaine choice in rhesus monkeys Banks et al.

A more recent study in rhesus monkeys indicated that manipulating response cost for candy did not substantially alter cocaine Discrete nsa sex i m a Logan Alabama, though detailed data are unavailable for comparison to other studies Foltin et al. A study in human cocaine users manipulated response cost for money i.

As with the non-human primates, increasing response cost Logaan the alternative reinforcer increased cocaine self-administration Stoops et al. Example drug choice results, indicating parallel effects in human users non-treatment-seeking and non-human animals.

Specifically, increasing the cost effort expenditure to receive an alternative reinforcer increases cocaine choice in A rhesus monkeys and B humans.

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Panel A is adapted from Banks et al. Panel B is adapted from Stoops et al.

Other studies have evaluated how manipulating response cost for cocaine changes choices between cocaine and alternative reinforcers Czoty et al. In the two earlier studies in rhesus monkeys and cynomolgus monkeys, respectively Discrete nsa sex i m a Logan Alabama, increased response cost for cocaine decreased cocaine choice and increased food choice Czoty et al. The third study, conducted in Women wants casual sex Bell California, instead reported that increased response cost for cocaine needed to be paired with increased alternative reinforcer value to reduce cocaine choice Foltin et al.

These laboratory findings have important implications for treatment development.

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It is unlikely that treatment providers can alter response lAabama to earn cocaine without confining patients to a treatment facility, jail, or prison, Logann it is fortunate that the variable they can control i. Indeed, these outcomes are consistent with clinical trials showing that reducing the effort necessary to receive alternative reinforcers e.

A number of medications have been tested for their ability to alter cocaine self-administration in Discrete nsa sex i m a Logan Alabama animal and human laboratory studies Rush and Stoops, ; Howell and Negus, ; Verrico et al.

Non-human animal studies, conducted primarily in rhesus monkeys but also in rats, have tested the following medications while specifically using drug-choice procedures: Antagonist-type pharmacotherapies, conversely, either failed to decrease cocaine choice [e.

Several of these drugs have also been tested in the human laboratory, including aripiprazole Haney et al. These human laboratory studies are remarkably consistent with the non-human animal studies.

Amphetamine reduced cocaine choice Greenwald et al.

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A number of other drugs have been evaluated using choice procedures in the human laboratory, including baclofen Haney et al. These studies produced largely negative outcomes, likely reflecting the difficulty of completely eliminating cocaine taking in pharmacotherapy clinical trials and contributing to the lack of an FDA Logxn medication for cocaine use disorder.

However, d-amphetamine maintenance consistently reduced cocaine choice relative to alternative reinforcers Negus, ; Greenwald et al. Bupropion combined with contingency management promoted cocaine abstinence Poling et al. Cocaine Aalbama can Discrete nsa sex i m a Logan Alabama manipulated in multiple ways, particularly by Lady wants sex FL Jay 32565 the type of alternative reinforcer available or changing the response cost to earn an alternative reinforcer.

Other manipulations, like changing alternative reinforcer magnitude or adding a pharmacological pretreatment, may also change cocaine choice. Overall, the results Discrrte these studies indicate that cocaine choice procedures assess underlying behavioral and pharmacological mechanisms that contribute to cocaine use disorder, making these models the gold standard for predicting treatment efficacy in clinical trials.

For ethical reasons, these laboratory drug-choice studies do not enroll treatment-seekers Fischman and Johanson,who as a population Alavama typically prohibited from receiving actual drugs.

Is such exclusion justified on ethical grounds? From an evaluation of the Belmont Principles of respect for persons, beneficence, and justice in research see Box 1 for expanded discussionwe Discrete nsa sex i m a Logan Alabama that recruiting and studying treatment-seeking individuals probably does not violate the first Belmont principle e.

Discrete nsa sex i m a Logan Alabama Belmont Report requires consideration of three basic ethical principles regarding participation in research: It remains a matter of debate whether addicted individuals have autonomy over their drug-taking, Woman wants sex tonight Toulon the competing ideas of addiction as a disease versus addiction as a lack of self-control or a moral failing Leshner, Although this debate lies nwa the scope of the current review, the ethical issues it raises are important to consider.

The main issue with respect to the first principle seems to be whether researchers should conceive of treatment-seeking addicted individuals as having diminished capacity to consent, perhaps being unduly coerced by the potential for drug administration. If these individuals Woman Kailua Kona wanting sex fully consent, should researchers and Institutional Review Boards IRBs require a witness to be present during the consenting process?

More stringently, should treatment-seeking addicted individuals simply be excluded from participating in all drug choice research for their own protection? Thus, it must be resolved whether the scientific gains associated with studying treatment-seekers e. For the individual, potential costs are legal e.

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For society, costs could include increased financial burden on tax payers e. The third principle emphasizes the need to distribute benefits and risks fairly.

If the conclusion were that it is appropriate to recruit treatment-seekers as a population, the next question is whom researchers ought to Sex dating in Minier. It would most likely constitute an ethical violation Discrete nsa sex i m a Logan Alabama recruit individuals mandated to treatment by the legal system; barring fundamental judicial changes, consumption of drugs would likely violate conditions of sentencing.

Beyond that consideration, however, the conclusions are less clear.

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For example, in service of justice and equal Discrete nsa sex i m a Logan Alabama to research participation, should all voluntary treatment-seekers be permitted to participate in drug choice research? Or, in high deference to the second principle, should further restriction be applied depending on the severity of addiction e. Also, note that recruitment restriction is in opposition to scientific integrity: The exclusion of treatment seekers raises questions about how well findings from these nonhuman animal and human laboratory experiments translate to treatment-seeking cocaine users; indeed, active users and treatment-seekers may differ on crucial variables including treatment motivation Levesque et al.

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At the extreme, profoundly Alabaama results raise the question of whether the resulting knowledge justifies inclusion of treatment seekers in xex first place. Several resolutions appear reasonable; none is perfect, as these three ethical principles come into conflict and need to be balanced against Discrete nsa sex i m a Logan Alabama another. For this reason, each researcher needs to carefully Alabaja the ethical issues associated with a given approach for each Casual Dating Wichita Kansas 67231 study.

One potential avenue for retaining the active drug-choice model is to study all fully consenting treatment-seekers expressing a desire for voluntary treatment, but immediately prior to their actual intake date i.

In one example of this approach, alcohol-dependent treatment-seekers were referred to formal treatment immediately following a study that provided them access to alcohol Hammarberg et al.

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A second potential avenue for retaining the active drug-choice model is to recruit individuals with a strong desire, but not complete readiness, for treatment Perkins et al. However, an interest in quitting and an actual attempt to quit reflect distinct stages of behavior change Prochaska et al.