Unpredictable availability as a determinant of drug-related outcomes

不可预测的可用性是药物相关结果的决定因素

基本信息

批准号：
10360602
负责人：
Sally Huskinson
金额：
$ 36.81万
依托单位：
UNIVERSITY OF MISSISSIPPI MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2025-03-31
项目状态：
未结题

项目摘要

Project Summary Unpredictable drug access may play an important role in drug abuse. We know from laboratory studies that behavior maintained by nondrugs such as food is more persistent with unpredictable (i.e., variable) schedules of availability than with predictable (i.e., fixed) schedules, and nonhuman subjects choose a variable option over a fixed one even when it costs more in terms of responses per delivery. We recently found that rhesus monkeys choose variable cocaine over a fixed cocaine option, extending work with nondrug reinforcers to a drug of abuse. In addition, we have preliminary data showing that a history of responding for cocaine injections under a variable schedule increases cocaine self-administration under a progressive-ratio schedule. Thus, we predict that unpredictable access to drugs of abuse is an important determinant of the choice to take a drug at the expense of nondrug alternatives and that a history of unpredictable drug access can in- crease the reinforcing effectiveness of drugs. In Specific Aim 1, we will use drug vs. nondrug choice to evaluate the prediction that cocaine choice will be greatest when it is delivered under an unpredictable sched- ule and food under a predictable schedule. Conversely, cocaine choice will be decreased when food is deliv- ered under an unpredictable schedule and cocaine under a predictable schedule. Confirmation of our hypothe- ses would indicate that unpredictable availability contributes to excessive allocation of behavior toward procur- ing drugs at the expense of more predictable, nondrug alternatives. If unpredictable food delivery decreases cocaine choice, it would support the use of novel and easily implemented modifications to therapies like con- tingency management or treatments that incorporate nondrug reinforcers. In Specific Aim 2 we hypothesize that long-term exposure to a variable schedule of cocaine delivery will increase the effectiveness of cocaine as a reinforcer relative to a period of fixed cocaine exposure, and this effect will be enhanced with a more unpre- dictable VR compared to a more predictable VR. Confirmation of this prediction would indicate that unpredicta- bility is a contributing factor to the perseverative drug-seeking behavior seen in cocaine-dependent individuals. The data collected in this aim will allow us to evaluate whether placing drug reinforcers under more predictable schedules (as is experienced with agonist replacement therapy) can reduce some of the deleterious effects of a history of unpredictable access. A reduction in adverse consequences engendered by a switch from unpre- dictable to predictable schedules may represent a behavioral mechanism underlying agonist replacement ther- apies. Conversely, we will be able to evaluate whether placing a drug with a history of predictable access un- der unpredictable-access conditions exacerbates drug-seeking behavior, which would have implications for effects of discontinuing agonist replacement therapy or prescription drug availability which would represent a transition from predictable drug access to unpredictable drug access (i.e., returning to illicit drug use).

项目概要我们从实验室研究中得知，不可预测的药物获取可能在药物滥用中发挥重要作用。通过食物等非药物维持的行为在不可预测（即可变）的时间表下更加持久与可预测（即固定）时间表相比，可用性更高，并且非人类受试者选择可变选项即使每次交付的响应成本更高，我们最近发现恒河猴也超过了固定的。猴子选择可变可卡因而不是固定可卡因选项，将非药物强化剂的作用扩展到了此外，我们有初步数据显示对可可注射有反应的历史。在可变时间表下增加可卡因的自我管理在渐进比例时间表下。预测滥用药物的不可预测性是选择采取药物治疗的一个重要决定因素以牺牲非药物替代品为代价的药物，并且不可预测的药物获取历史可能会导致 - 在具体目标 1 中，我们将使用药物与非药物的选择来增强药物的有效性。评估可可选择在不可预测的时间表下交付时将是最佳选择的预测在可预测的离线时间安排和食物下，当食物交付时可卡因的选择将会减少。在不可预测的时间表下，可可在可预测的时间表下证实了我们的假设。 ses 将表明不可预测的可用性导致采购行为的过度分配如果不可预测的食物供应减少，就会以牺牲更可预测的非药物替代品为代价。可卡因的选择，它将支持使用新颖且易于实施的疗法修改，例如反包含非药物强化剂的应急管理或治疗。长期采用可变的可可交付时间表将提高可可的有效性，因为相对于一段时间的固定可可暴露而言，这种效果会随着更意想不到的情况而增强。可预测的 VR 与更可预测的 VR 相比。这一预测的确认将表明不可预测的能力是可可依赖者持续寻求药物行为的一个促成因素。为此目的收集的数据将使我们能够评估是否将药物增强剂置于更可预测的范围内时间表（正如激动剂替代疗法所经历的那样）可以减少某些有害影响不可预知的访问历史，减少因突然改变而造成的不利后果。可预测的时间表可能代表了激动剂替代疗法背后的行为机制 apies 是不可见的，我们将能够评估是否将具有可预测访问历史的药物置于不可见状态。不可预测的获取条件会恶化寻求毒品的行为，这将对停止激动剂替代疗法或处方药可用性的影响，这将代表从可预测的药物获取转变为不可预测的药物获取（即返回非法药物使用）。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Quantification of observable behaviors induced by typical and atypical kappa-opioid receptor agonists in male rhesus monkeys.

雄性恒河猴中典型和非典型 kappa-阿片受体激动剂诱导的可观察行为的量化。

DOI：
发表时间：
2020-07
期刊：
影响因子：
3.4
作者：
Huskinson, S L;Platt, D M;Brasfield, M;Follett, M E;Prisinzano, T E;Blough, B E;Freeman, K B
通讯作者：
Freeman, K B

Kappa opioid agonists reduce oxycodone self-administration in male rhesus monkeys.

Kappa 阿片类激动剂可减少雄性恒河猴的羟考酮自我给药。

DOI：
发表时间：
2020-05
期刊：
影响因子：
3.4
作者：
Zamarripa, C Austin;Naylor, Jennifer E;Huskinson, Sally L;Townsend, E Andrew;Prisinzano, Thomas E;Freeman, Kevin B
通讯作者：
Freeman, Kevin B

Unpredictability as a modulator of drug self-administration: Relevance for substance-use disorders.

作为药物自我给药调节剂的不可预测性：与物质使用障碍的相关性。

DOI：
发表时间：
2020-09
期刊：
影响因子：
1.3
作者：
Huskinson; Sally L
通讯作者：
Sally L

Quantification of observable behaviors following oral administration of oxycodone and nalfurafine in male rhesus monkeys.

雄性恒河猴口服羟考酮和纳芙拉芬后可观察到的行为的量化。

DOI：
发表时间：
2023-11-01
期刊：
影响因子：
4.2
作者：
Huskinson, Sally L;Platt, Donna M;Smith, Zachary R;Doyle, William S;Zamarripa, C Austin;Dunaway, Kristen;Prisinzano, Thomas E;Freeman, Kevin B
通讯作者：
Freeman, Kevin B

Challenges to Conducting Contingency Management Treatment for Substance Use Disorders: Practice Recommendations for Clinicians.

对药物使用障碍进行应急管理治疗的挑战：给临床医生的实践建议。