CONTROL OF BEHAVIOR BY DRUG INJECTION

人类滥用的大多数药物都可以作为积极的增强剂来维持 并加强导致它们在动物身上使用的行为。 正在进行实验，以评估神经药理学和 寻毒和吸毒行为的行为机制 对大鼠和猴子的药理学或行为学能力 通过操纵来改变这种行为。目前，研究的重点是 可卡因、冰毒和尼古丁。在一系列研究中， 我们已经证明，将两种歧视性刺激相结合与 相同增强剂对该增强剂的响应增加2-3 折叠，不管增强剂是食物，水，还是休克- 回避或吸食可卡因。组合与两个不同的刺激相关的刺激 食物和水等食欲增强剂也会增加 回应，尽管程度不同。我们最近展示了 与可卡因自我给药类似的效果，在结合 与可卡因和食物强化相关的刺激导致增加 正在回应。这些结果支持了这样一种假设，即 与来自同一激励类别的增强剂相关的两个刺激 (食欲)是相互促进的。因此，在某些情况下， 与替代增强剂相关的刺激可能会增加 自我管理可卡因的动机。在另一系列研究中， 我们正在评估慢性疾病后的神经适应性变化。 甲基苯丙胺对大鼠的自我给药 多巴胺摄取部位和D1和D2受体，以及摄取和 其他神经递质系统在不同时间的受体位置 在停止使用甲基苯丙胺之后。调查结果支持 关于多巴胺能神经传递功能减退的假说 在长期接触甲基苯丙胺期间，当甲基苯丙胺被揭发时 停药，表明阿片类药物和5-羟色胺能参与其中 系统。在另一项研究中，我们正在评估 在什么情况下静脉注射。尼古丁通过以下途径维持自我给药 以及接触其他药物如何影响猴子的这种行为 比如咖啡因。最后，给出了复杂的静脉注射二次规划。药物 注射，其中长的行为链由高度的 罕见的药物注射正被用来研究动机 与可卡因或可卡因等药物有关的刺激的性质 冰毒。由于二阶时间表在许多情况下是相似 为人类的毒品寻觅行为提供了一种相对 未受污染的措施，如“毒瘾”现象，使用这些 评估药理学和行为学方法减少 寻求毒品的行为也将对 预防与药物滥用有关的艾滋病毒传播。

Most drugs which humans abuse serve as positive reinforcers to maintain and strengthen behavior leading to their administration in animals. Experiments are being conducted to assess neuropharmacological and behavioral mechanisms underlying drug-seeking and drug-taking behavior in rats and monkeys and the ability of pharmacological or behavioral manipulations to modify such behavior. Currently, studies are focusing on cocaine, methamphetamine and nicotine. In one series of studies, we have shown that combining two discriminative stimuli associated with the same reinforcer increases responding for that reinforcer by 2-3 fold, regardless of whether the reinforcer was food, water, shock- avoidance or cocaine. Combining stimuli associated with two different appetitive reinforcers, such as food and water, also increases responding, although not to the same degree. We have recently shown a similar effect with cocaine self-administration, where combining stimuli associated with cocaine and food reinforcement led to increased responding. These results support the hypothesis that the effects of two stimuli associated with reinforcers from the same incentive class (appetitive) are mutually enhancing. Thus, in some situations a stimulus associated with an alternative reinforcer might increase the motivation to self-administer cocaine. In another series of studies, we are assessing neuroadaptive changes that follow chronic methamphetamine self-administration by rats by evaluating densities of dopamine uptake sites and D1 and D2 receptors, as well as uptake and receptor sites for other neurotransmitter systems, at various times after ceasing access to methamphetamine. Findings support the hypothesis of a functional reduction of dopaminergic neurotransmission during chronic methamphetamine exposure, unmasked when methamphetamine is withdrawn, and indicate involvement of opioid and serotonergic systems. In yet other studies, we are evaluating the range of conditions under which i.v. nicotine maintains self-administration by monkeys and how such behavior is influenced by exposure to other drugs such as caffeine. Finally, complex second-order schedules of i.v. drug injection in which long chains of behavior are maintained by highly infrequent injections of drug are being used to study motivational properties of stimuli associated with drugs such as cocaine or methamphetamine. Since second-order schedules are analogous in many ways to human drug-seeking behavior and may provide a relatively uncontaminated measure of phenomena such as "drug craving," using these procedures to evaluate pharmacological and behavioral means of reducing drug-seeking behavior will also have important implications for prevention of HIV transmission related to drug abuse.