Human d-amphetamine drug discrimination: methamphetamine and hydromorphone.

Standard measures of subjective and discriminative effects of drugs were compared in 5 human volunteers. Subjects responded on a second-order color-tracking procedure, where 30 mg of d-amphetamine served as a discriminative stimulus for one response and its absence as the discriminative stimulus for another response. Self-reported subjective effects were assessed concurrently using the single-dose questionnaire, subscales of the Addiction Research Center Inventory, and several analogue rating scales. On different days following discrimination acquisition, varying doses of d-amphetamine, methamphetamine, and hydromorphone were administered. In these test sessions, either response was reinforced. Methamphetamine and d-amphetamine occasioned dose-related increases in d-amphetamine appropriate responding; hydromorphone did not. Methamphetamine and d-amphetamine occasioned dose-related increases in reports of the drug received being most like "speed"; hydromorphone occasioned dose-related increases in reports of the drug received being most like "dope." All three drugs occasioned dose-related increases in reports of drug liking, and increases in the morphine-benzedrine group, amphetamine, and benzedrine group scales of the Addiction Research Center Inventory. This experiment demonstrated that although explicit discriminative control of behavior by a drug may covary with drug identification, it does not necessarily covary with other self-reported subjective effects. Thus, the complementary nature of the data provided by drug discrimination and standard subjective-effects measures provides quantitative and qualitative data useful in studying both relatively novel compounds and the behavioral biology of psychoactive drugs in general.     

Effect of drugs on response-duration differentiation VII: response-force requirements

Rats were trained to press a lever for at least 1 s but for less than 1.3 s. The force required to press the lever was then increased or decreased by 10, 15, or 20 g. Increases in the force requirements for lever pressing decreased timing accuracy, but decreases in the force requirement had the opposite effect. Accuracy decreases at increasing force requirements were characterized by an increase in the relative frequency of responses that were too short to meet the reinforcement criterion. In contrast, increases in accuracy when the force requirements were decreased were characterized by increases in response durations that met the reinforcement criterion and decreases in the relative frequency of responses that were too short to produce the reinforcer. Phencyclidine (PCP) and methamphetamine produced dose-dependent decreases in accuracy that were associated primarily with increases in the relative frequency of short response durations, although methamphetamine also produced increases in long response durations at some doses. When the effects of PCP were determined with the force requirement increased by 10 g or decreased by 15 g, the cumulative response-duration distribution shifted toward even shorter response durations. When the effects of methamphetamine were determined with the force requirement on the lever increased by 10 g, the cumulative frequency distribution was shifted toward shorter response durations to about the same extent as it had been before force requirements increased; however, when the force required to press the lever was decreased by 15 g, these shifts toward shorter response durations almost completely disappeared. These results show that increases and decreases in the force requirements for lever pressing have different effects on the accuracy of temporal response differentiation.     

Drug discrimination under two concurrent fixed-interval fixed-interval schedules

Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which the FI component with the shorter time requirement reinforced responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66% (after pentobarbital) to 68% (after saline) of their reinforcers for responding under the FI 100-s component of the concurrent schedule. These birds made an average of 70% of their responses on both the pentobarbital-biased key after the training dose of pentobarbital and the saline-biased key after saline. After responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons earned an average of 67% of their reinforcers for responding under the FI 40 component after both saline and the training dose of pentobarbital. These birds made an average of 75% of their responses on the pentobarbital-biased key after the training dose of pentobarbital, but only 55% of their responses on the saline-biased key after saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response curves were similar under these two concurrent schedules. Pentobarbital, chlordiazepoxide, and ethanol produced dose-dependent increases in responding on the pentobarbital-biased key as the doses increased. For some birds, at the highest doses of these drugs, the dose-response curve turned over. Increasing doses of phencyclidine produced increased responding on the pentobarbital-biased key in some, but not all, birds. After methamphetamine, responding was largely confined to the saline-biased key. These data show that pigeons can perform drug discriminations under concurrent schedules in which the reinforcement frequency under the schedule components differs only by a factor of two, and that when other drugs are substituted for the training drugs they produce dose-response curves similar to the curves produced by these drugs under other concurrent interval schedules.     

Optimizing Contingency Management With Methamphetamine-Using Men Who Have Sex With Men

Among men who have sex with men (MSM), methamphetamine use is associated with multiple, overlapping syndemic conditions including increased risk for HIV seroconversion and onward HIV transmission. Contingency management (CM) is an evidence-based behavioral intervention implemented to curb methamphetamine use and optimize HIV/AIDS prevention among MSM in San Francisco since 2003. We conducted a program evaluation to document the evolution of this 12-week CM program to include delivery of brief, individual counseling incorporating motivational interviewing and behavioral skills. A drop-in group delivered concurrently with CM urine-screening visits also provides peer support as well as referrals for other social and medical services. From December 2011–October 2013, a total of 131 clients enrolled in the CM program and provided a median of 22 urine samples (Interquartile Range = 10–34) that were nonreactive for methamphetamine. Findings support the feasibility and acceptability of integrating individual and group counseling with community-based CM for methamphetamine-using MSM.     

Effects of methamphetamine and scopolamine on variability of response location.

Methamphetamine and scopolamine were studied in monkeys responding under a multiple fixed-ratio fixed-interval schedule of reinforcement. A response on any one of six levers could satisfy the schedule requirements. Variability of response location was evaluated in terms of switches, where a switch was defined as a response on one lever followed by a response on a different lever. Under baseline conditions the fixed-ratio schedule generated a high rate of responding and a low level of variability, while the fixed-interval schedule generated a low rate of responding and a high level of variability. Both methamphetamine (0.1 to 0.5 mg/kg) and scopolamine (2.4 to 240 microgram/kg) decreased overall response rate and increased variability of response location in each component of the multiple schedule with increasing doses of drug. At lower doses both drugs were found to decrease rate without affecting response variability.     

冰毒使用者抑制控制的损伤、可逆性及干预策略

冰毒使用的危害日益凸显,受到社会的普遍关注。行为、认知和脑功能的研究结果一致表明:长期的冰毒使用会导致使用者的抑制控制受损,包含一般抑制控制损伤以及药物相关线索条件下的损伤。这些损伤与前额脑区的异常密切相关,对冰毒使用者的行为和认知能力产生不良影响。目前,这些损伤只能部分恢复,因此,改善冰毒使用者抑制控制的干预策略成为热点。未来研究可以从不同药物成瘾者的差异性、多药物使用模式以及有区别的运动干预等方面对冰毒使用者的抑制控制损伤进行深入研究。     

Behavioral pharmacology of the odor span task: Effects of flunitrazepam,ketamine, methamphetamine and methylphenidate

The Odor Span Task is an incrementing non‐matching‐to‐sample procedure that permits the study of behavior under the control of multiple stimuli. Rats are exposed to a series of odor stimuli and selection of new stimuli is reinforced. Successful performance thus requires remembering which stimuli have previously been presented during a given session. This procedure has been frequently used in neurobiological studies as a rodent model of working memory; however, only a few studies have examined the effects of drugs on performance in this task. The present experiments explored the behavioral pharmacology of a modified version of the Odor Span Task by determining the effects of stimulant drugs methylphenidate and methamphetamine, NMDA antagonist ketamine, and positive GABA_A modulator flunitrazepam. All four drugs produced dose‐dependent impairment of performances on the Odor Span Task, but for methylphenidate and methamphetamine, these occurred only at doses that had similar effects on performance of a simple odor discrimination. Generally, these disruptions were based on omission of responding at the effective doses. The effects of ketamine and flunitrazepam were more selective in some rats. That is, some rats tested under flunitrazepam and ketamine showed decreases in accuracy on the Odor Span Task at doses that did not affect simple discrimination performance. These selective effects indicate disruption of within‐session stimulus control. Overall, these findings support the potential of the Odor Span Task as a baseline for the behavioral pharmacological analysis of remembering.     

Finding Sunshine on a Cloudy Day: A Positive Affect Intervention for Co-Occurring Methamphetamine Use and HIV

Among sexual minority men (i.e., gay, bisexual, and other men who have sex with men) living with HIV, those who use methamphetamine experience profound health disparities. Affect Regulation Treatment to Enhance Methamphetamine Intervention Success (ARTEMIS) is an evidence-based, 5-session, individually delivered positive affect intervention adapted for sexual minority men living with HIV who use methamphetamine. ARTEMIS was designed to amplify the benefits of evidence-based substance use interventions such as contingency management (CM) with this high-priority population. Delivering ARTEMIS during CM has been shown to assist participants in reducing stimulant use, increasing positive affect, and achieving durable reductions in HIV viral load. We describe the theoretical underpinnings of the ARTEMIS intervention, provide details of the training and session protocols with a case example, and discuss implications for future applications in research and clinical settings.