Individual differences that may contribute to vulnerability to abuse drugs have been identified. Sensation-seeking status has been shown to influence both vulnerability to drug use and response to acute drug administration. The purpose of the present experiment was to examine the reinforcing effects of d-amphetamine in high and low sensation-seeking subjects using a modified progressive-ratio procedure. A battery of subject-rated, performance, and cardiovascular measures was also included to better characterize the effects of d-amphetamine in these groups. Ten high sensation seekers and ten low sensation seekers that were matched for education, age, drug use, height, and weight, first sampled doses of d-amphetamine (0, 8, and 16 mg). In subsequent sessions, subjects were offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. d-Amphetamine functioned as a reinforcer and produced prototypical stimulant-like effects (e.g., increased subject-ratings of Like Drug, enhanced performance, and increased heart rate). High sensation seekers were more sensitive than low sensation seekers to the reinforcing and some of the subject-rated effects of d-amphetamine. The results of the present experiment extend those of previous findings by demonstrating that the reinforcing effects of damphetamine vary as a function of the biologically based sensation-seeking personality trait. These results suggest that increased stimulant drug use and abuse among high sensation seekers may be related, in part, to increased sensitivity to the reinforcing effects of stimulants among these individuals.

Few studies have simultaneously evaluated delay discounting and behavioral economic demand to determine their unique contribution to drug use. A recent study in cannabis users found that monetary delay discounting uniquely predicted cannabis dependence symptoms, whereas cannabis demand uniquely predicted use frequency. This study sought to replicate and extend this research by evaluating delay discounting and behavioral economic demand measures for multiple commodities and including a use quantity measure. Amazon.com’s Mechanical Turk was used to sample individuals reporting recent cannabis use (n = 64) and controls (n = 72). Participants completed measures of monetary delay discounting as well as alcohol and cannabis delay discounting and demand. Cannabis users and controls did not differ on monetary delay discounting or alcohol delay discounting and demand. Among cannabis users, regression analyses indicated that cannabis delay discounting uniquely predicted use severity, whereas cannabis demand uniquely predicted use frequency and quantity. These effects remained significant after controlling for other delay discounting and demand measures. This research replicates previous outcomes relating delay discounting and demand with cannabis use and extends them by accounting for the contribution of multiple commodities. This research also demonstrates the ability of online crowdsourcing methods to complement traditional human laboratory techniques.

The results of animal research suggest that the use of partial agonists at dopamine (DA) D 2 receptors may be an effective strategy for the treatment of stimulant dependence. Aripiprazole is an atypical antipsychotic that has partial agonist activity at D 2 receptors. In this experiment, seven human participants with a history of nontherapeutic stimulant use learned to discriminate 15 mg oral D-amphetamine. After acquiring the discrimination (ie X80% correct responding on four consecutive sessions), the effects of a range of doses of Damphetamine (0, 2.5, 5, 10, and 15 mg), alone and in combination with aripiprazole (0 and 20 mg), were assessed. D-Amphetamine alone functioned as a discriminative stimulus, produced prototypical subject-rated drug effects (eg increased ratings of Active, Alert, Energetic) and elevated cardiovascular indices. These effects were generally a function of dose. Aripiprazole alone did not occasion D-amphetamineappropriate responding or produce subject-rated effects, but modestly impaired performance. Administration of aripiprazole significantly attenuated the discriminative-stimulus and cardiovascular effects of D-amphetamine, as well as some of the subject-rated drug effects. These data are consistent with previous preclinical findings and suggest that DA partial agonists deserve further evaluation as potential pharmacotherapies in the management of stimulant dependence. Future studies should investigate the ability of aripiprazole or related compounds to attenuate the behavioral effects of stimulants associated with a greater degree of dependence, such as methamphetamine or cocaine, in dependent individuals.

The findings of the present experiment demonstrate that modafinil can function as a reinforcer and that the reinforcing effects of modafinil are influenced by behavioral demands following drug administration, similar to those of other stimulant drugs.

This study was undertaken to investigate pharmacological variables that influence the reinforcing efficacy of psychostimulants. Rhesus monkeys (n ϭ 9) responded under a withinsession, exponentially increasing, progressive ratio schedule of cocaine reinforcement. Doses of cocaine, methylphenidate (MP), cocaine analogs [(Ϯ)-2␤-propanoyl-3␤-(2-naphthyl)-tropane (WF-23), HD-23; (Ϯ)-2␤-propanoyl-3␤-(2-isopropenyl)-tropane (WF-60), HD-60; and 2␤-propanoyl-3␤-(4-tolyl)-tropane (HD-11, WF-11), and 2␤-propanoyl-3␤-(4-tolyl)-tropane (HD-11, WF-11), PTT], and MP analogs [(␣R,2R)-␣-(2-naphthalenyl)-2-piperidineacetic acid methyl ester, HDMP-28; and (␣R,2S)-␣-(2-naphthalenyl)-2-pyrrolideneacetic acid methyl ester, HDMP-29] that varied in their pharmacokinetic and pharmacodynamic properties were substituted for cocaine. These drugs were chosen according to their selectivity for dopamine transporters (DAT) and 5-hydroxytryptamine (serotonin) transporters (5-HTT) as assessed in rodents and their duration of action. In addition, data pertaining to the rate of onset at DAT were collected for the cocaine analogs using an ex vivo binding assay in rodent tissue. Finally, the pharmacodynamic profile of select drugs was confirmed in primate brain tissue. All drugs had reinforcing effects except HDMP-29. The rank ordering of the peak breaking points (BPs) was cocaine ϭ MP ϭ HDMP-28 Ն HD-60 Ն PTT Ն HD-23 Ͼ HDMP-29. The time to peak DAT occupancy for the cocaine analogs was greater than 30 min. The potency to maintain peak BP was significantly correlated with DAT affinity. There was not a linear relationship between monoamine transporter affinity and reinforcing efficacy, but it appeared that in nonhuman primates there is a range of DAT affinity under which maximal responding is maintained. Interestingly, the 5-HTT-selective cocaine analog HD-60 functioned robustly as a reinforcer at several doses in all monkeys tested. These data question the dogma regarding the role of pharmacokinetic factors and the relative influence of DAT and 5-HTT in stimulant reinforcement.Although the use of psychomotor stimulants such as cocaine and various amphetamine derivatives has remained stable over the past several years (SAMHSA, 2001), an effective pharmacotherapy has yet to be developed. An understanding of the pharmacological properties that mediate the abuse liability of these drugs will assist in the design of treatments for psychostimulant abuse and dependence and result in a better understanding of addiction. Animal models of drug self-administration have allowed for the systematic investigation of drug-reinforced behavior; however, the variables that influence the reinforcing efficacy of psychostimulants are still not fully understood.One pharmacological attribute common to psychostimu-