Choice between money and intranasal heroin in morphine-maintained humans

Five morphine-maintained individuals participated in an inpatient study evaluating the effects of a monetary alternative ($10, $20, $40) on intranasal (i.n.) heroin (placebo, 12.5, 25, 50, 100 mg) self-administration, using a procedure in which subjects chose between money and heroin. Each money amount was tested in combination with each heroin dose. Subjects responded under a progressive-ratio schedule (PR 50, 100, ..., 2800); the PR value increased independently for each option. Subjective, performance, and physiological effects were also measured during each session. Heroin breakpoint values increased in a dose-related manner, relative to placebo, when $10 or $20 was available. In contrast, only the highest dose produced a heroin breakpoint value that was significantly different from placebo when $40 was available. Heroin also produced dose-related increases in several ratings of drug effect, including "I feel ..." "a good drug effect", "high", "mellow", and "stimulated". These effects were not significantly affected by the alternative money condition. These results demonstrated: (1) the dose-related reinforcing effects of i.n. heroin in opioid-dependent individuals; (2) that i.n. heroin self-administration can be modified by the availability of an alternative reinforcer (i.e. money); and (3) that self-reported drug effects can be differentiated from drug self-administration.     

Delay discounting of cocaine by rhesus monkeys.

The present, subjective value of a reinforcer typically decreases as a function of the delay to its receipt, a phenomenon termed delay discounting. Delay discounting, which is assumed to reflect impulsivity, is hypothesized to play an important role in drug abuse. The present study examined delay discounting of cocaine injections by rhesus monkeys. Subjects were studied on a discrete-trials task in which they chose between 2 doses of cocaine: a smaller, immediate dose and a larger, delayed dose. The immediate dose varied between 0.012 and 0.4 mg/kg/injection, whereas the delayed dose was always 0.2 mg/kg/injection and was delivered after a delay that varied between 0 and 300 s in different conditions. At each delay, the point at which a monkey chose the immediate and delayed doses equally often (i.e., the ED50) provided a measure of the present, subjective value of the delayed dose. Dose-response functions for the immediate dose shifted to the left as delay increased. The amount of the immediate dose predicted to be equal in subjective value to the delayed dose decreased as a function of the delay, and hyperbolic discounting functions provided good fits to the data (median R2 = .86). The current approach may provide the basis for an animal model of the effect of delay on the subjective value of drugs of abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of sex, estrous cycle, and drug-onset age on cocaine self-administration in rats (Rattus norvegicus).

The influence of sex, phase of the estrous cycle, and age of drug onset on cocaine self-administration was examined. Adult male, adult female, and adolescent male rats (Rattus norvegicus) were evaluated using low fixed-ratio (FR) schedules of drug delivery with a single fixed cocaine unit dose or a range of cocaine unit doses with a single FR schedule. Sex differences in adults were observed for mg/kg consumption of the 3.0-mg/kg unit dose, with consumption being significantly less in estrus females than in males. Over the estrous cycle, mg/kg consumption of this unit dose was significantly less during estrus than during metestrus-diestrus. Differences due to age of drug onset were also observed, with mg/kg consumption of the 3.0-mg/kg unit dose being significantly less in adolescent males than adult males or adult females during metestrus-diestrus. In contrast, these various groups did not have significantly different mg/kg intakes of cocaine unit doses     

The effects of memantine on the subjective, reinforcing and cardiovascular effects of cocaine in humans

Eight male frequent cocaine smokers participated in a 44- to 47-day inpatient and outpatient study to assess the effects of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, memantine, on cocaine self-administration, subjective effects, and psychomotor performance. Participants were maintained on memantine (0 and 20 mg daily) for 7-10 days prior to laboratory testing, using a double-blind crossover design. Under each medication condition, participants smoked four doses of cocaine base (0, 12, 25 and 50 mg), and were subsequently given five opportunities, 14 min apart, to self-administer that dose of cocaine or receive a merchandise voucher ($5.00). Each cocaine dose was tested twice under each medication condition, and the order of medication condition and cocaine dose was systematically varied. Vital signs were recorded every 2 min, and subjective effects were assessed at baseline and after each cocaine or voucher delivery. In addition, psychomotor performance was assessed before and after each self-administration session. Memantine maintenance was not associated with changes in psychomotor performance or the number of cocaine doses chosen each session. Memantine maintenance was, however, associated with significant increases in some subjective effects of cocaine, including ratings of 'good drug effect', 'high', 'potency', 'quality', and street value. These data suggest that NMDA antagonists may have limited usefulness as treatment medications for cocaine abuse.     

The effects of transnasal butorphanol on mood and psychomotor functioning in healthy volunteers

Transnasal butorphanol is effective in relieving migraine and postoperative pain. The extent to which this drug preparation impacts on cognitive and psychomotor performance, as well as mood, has not been examined. Accordingly, the cognitive and psychomotor, subjective, and physiological effects of two clinically relevant doses of transnasal butorphanol (1 and 2 mg) were compared to that of placebo, and a common analgesic drug combination given for pain relief in ambulatory settings, 600 mg of acetaminophen and 60 mg of codeine, in healthy volunteers (n = 10). The larger transnasal butorphanol dose impaired psychomotor performance for up to 2 h, and produced subjective effects for up to 3 h. The smaller dose had no psychomotor-impairing effects, but had subjective effects (including increased ratings of "sleepy"). All three active drug conditions including miosis. These laboratory results suggest that patients should use caution when using the 1-mg dose of transnasal butorphanol, and should curtail certain activities if they administer the 2-mg dose of transnasal butorphanol for analgesia.     

Reinforcing and Subjective Effects of Methylphenidate: Dose and Time in Bed.

So that reinforcing and subjective effects of methylphenidate as a function of dose and level of sleepiness could be evaluated, 21 volunteers received methylphenidate (5, 10, or 20 mg) or placebo on 2 sampling days. After 4 and 8 hr time in bed (TIB), they chose their preferred capsule on 5 days. Methylphenidate was chosen more frequently after 4 hr TIB (60%) than it was after 8 hr TIB (33%). The strongest preference (68%) was seen in the 10-mg group. At 10 and 20 mg, stimulant-like subjective effects were reported. The 10-mg group was more adversely affected by the restricted bedtime and showed more pronounced drug effects with methylphenidate. These results indicate that sleepiness modulates the reinforcing and subjective effects of methylphenidate. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opioid discrimination in humans: discriminative and subjective effects of progressively lower training dose

The purpose of this study was to examine the extent of covariation of subjective and discriminative drug effects as the dose of the discriminated training drug was progressively lowered. Six adult male volunteers with histories of opioid abuse, who were not currently physically dependent, were trained to discriminate the mu-receptor agonist hydromorphone (20 mg, oral) from placebo in daily sessions. They received financial reinforcement for correct responses. The hydromorphone training dose was then progressively reduced (20, 14, 10, 7, 5, and 3.5 mg) while the discrimination reinforcement contingencies remained in effect. Measures of subjective and physiological effects were concurrently collected during each discrimination session. As the training dose decreased, discriminative performance was generally well maintained, although the percent of drug-appropriate responses to hydromorphone did decline from 98% to 75%. The magnitude of the subjective and physiological effects of hydromorphone also decreased as the training dose decreased. At the lowest training dose, there were no physiological effects and few subjective effects of hydromorphone statistically different from placebo, although discrimination behavior remained statistically significant at all doses. These data indicate covariation of subjective effects and discrimination performance and suggest that discrimination behavior may be more sensitive for differentiating among drug conditions than traditional subjective effects measures.     

Detection of Legionella pneumophila in wastewater by nested polymerase chain reaction

Behavioral economics defines unit price (UP) as the ratio of the response requirement to magnitude of reinforcer. When applied to drug self-administration, the UP model defines UP as the ratio of the response requirement to the unit dose of drug. This model makes two predictions about drug self-administration: increasing UP decreases consumption and consumption at a given UP will be constant regardless of the response requirement and dose that make up the UP. In previous experiments conducted in rhesus monkeys allowed to choose between an i.v. injection of cocaine and food, the UP model has failed to adequately predict drug consumption in that consumption varied (increased with dose) at a given UP. However, previous experiments have allowed a fixed number of choice trials/day, thereby imposing a procedural ceiling on consumption that may have influenced conformity to the UP model. In the present experiment, the number of choice trials available was varied in such a way that constant drug consumption was possible over the range of UPs tested. The response requirement for cocaine was varied between 15 and 1200 lever presses/injection and the dose of cocaine was varied between 0.05 and 0.2 mg/kg/inj, yielding UPs from 300 to 5600 responses/mg/kg. The response requirement for food was always 30. As predicted by the UP model, cocaine consumption decreased as UP increased. Moreover, in contrast to previous experiments, consumption did not vary significantly across the response requirement/dose combinations that made up a UP. A detailed analysis suggested that a decrease in magnitude of the alternative reinforcer (one rather than three food pellets), rather than the increase in trials, was responsible for the improved conformity to the UP model in the present experiment relative to previous experiments. Taken together with previous experiments, the present experiment suggests that conformity to the UP model of drug consumption in a choice situation is dependent upon the magnitude of alternative reinforcers that are available. Consumption was best predicted by the UP model when the magnitude of the alternative reinforcer was small.     

Clinical pharmacology of buprenorphine: ceiling effects at high doses

OBJECTIVE: The purpose of this study was to characterize the acute effects of buprenorphine, an opioid partial mu-agonist, across a wide range of doses in comparison to methadone. METHOD: Healthy adult male volunteers, who had experience with but were not physically dependent on opioids, participated while residing on a closed research unit. Four subjects received buprenorphine (0, 1, 2, 4, 8, 16, and 32 mg sublingually and five subjects received methadone (0, 15, 30, 45, and 60 mg orally) in ascending order at 1-week intervals. Physiologic, subjective, and behavioral measures were monitored for 96 hours after drug administration. RESULTS: Both drugs produced typical opioid agonist effects (positive mood, sedation, respiratory depression, and miosis), some of which persisted for 24 to 48 hours. A plateau was observed for the dose effects of buprenorphine on subjective measures and respiratory depression. Pharmacokinetic data revealed that plasma concentrations of buprenorphine were linearly related to dose, indicating no limits on sublingual absorption in this dose range. CONCLUSIONS: This study shows a plateau on buprenorphine effects, consistent with its partial agonist classification, and that single doses of buprenorphine up to 70 times the recommended analgesic dose are well tolerated by nondependent humans.     

Comparing the subjective, psychomotor and physiological effects of intravenous nalbuphine and morphine in healthy volunteers

The purposes of this study were to characterize the subjective, psychomotor and physiological effects of nalbuphine in healthy non-drug abusing volunteers and to compare and contrast the effects of equianalgesic doses of nalbuphine and morphine. Subjects (12 males, 4 females) without histories of opiate dependence were injected in an upper extremity vein with 0, 2.5, 5.0 or 10 mg/70 kg nalbuphine, or with 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. The 10-mg doses of nalbuphine and morphine are considered equianalgesic and are doses commonly given for relief of postoperative pain. Subjective effects of nalbuphine included increased scores on the Pentobarbital-Chlorpromazine-Alcohol Group scale and the Lysergic Acid Diethylamide scale of the Addiction Research Center Inventory; increased adjective checklist ratings of "nodding," "numb" and "sweating"; increased visual analog scale ratings of "coasting or spaced out," "high" and "sleepy" and increased "feel drug effect" and drug-liking ratings. Ten milligrams of nalbuphine had subjective effects similar, and similar in magnitude, to those of 10 mg of morphine. Nalbuphine produced exophoria and impairment on the Digit Symbol Substitution Test in a dose-related fashion. Ten milligrams of morphine produced exophoria but did not affect performance on the Digit Symbol Substitution Test. Both nalbuphine and morphine induced miosis and decreases in respiration rate. The results of the present study demonstrate that 2.5 to 10 mg nalbuphine had orderly, dose-related effects on subjective, psychomotor and physiological variables. The results also indicate that 10 mg of nalbuphine produces a profile of subjective, psychomotor and physiological effects similar to that of an equianalgesic dose of morphine (10 mg). The similarity in profiles between drugs at this dose is consistent with both infrahuman studies, which suggests that nalbuphine is a mu agonist, and studies with nondependent opioid abusers, in which relatively low doses of nalbuphine (such as 10 mg) produce morphine-like effects.     

Reinforcing, subjective, and performance effects of lorazepam and diphenhydramine in humans.

The reinforcing. subjective. and performance effects of 400 mg diphenhydramine (D), 4 mg lorazepam (L), and placebo (P) were compared across repeated administrations in 12 healthy, adult male participants with histories of recreational sedative abuse. P, L, and D were administered orally in a block, random sequence 4 times each. L and D increased scores on participants liking of the drug, desire to take the drug again, and monetary value of the drug relative to placebo. D increased ratings on scales of unpleasant somatic side effects. When the choice was between D and P or between L and P, choice between D and L was greater than chance, and choice of P was less than chance. When the choice was between D and L, both drugs were chosen an equal number of times. L and D effects were consistent across repeated administrations. Correlational analysis showed that some subjective measures were positively correlated, whereas other measures were negatively correlated with measures of drug reinforcement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pharmacokinetics, safety, and tolerability of ascending single doses of moxifloxacin, a new 8-methoxy quinolone, administered to healthy subjects

The pharmacokinetics of moxifloxacin were investigated in six studies after oral administration of 50, 100, 200, 400, 600, and 800 mg. Eight healthy male volunteers were included in each study. With doses of up to 200 mg the study was performed as a double-blind, randomized group comparison (n = 6 verum and n = 2 matched placebo); with the higher doses the study was conducted with a double-blind, randomized, crossover design. Safety and tolerability were assessed by evaluation of vital signs, electrocardiograms, electroencephalograms, clinical chemistry parameters, results of urinalysis, and adverse events. The drug was well tolerated. The concentrations of moxifloxacin in plasma, urine, and saliva were determined by a validated high-pressure liquid chromatography assay with fluorescence detection. In addition, plasma and urine samples were analyzed by a bioassay. A good correlation between both methods was seen, indicating an absence of major active metabolites. The mean maximum concentrations of moxifloxacin in plasma (Cmax) ranged from 0.29 mg/liter (50-mg dose) to 4.73 mg/liter (800-mg dose) and were reached 0.5 to 4 h following drug administration. After reaching the Cmax, plasma moxifloxacin concentrations declined in a biphasic manner. Within 4 to 5 h they fell to about 30 to 55% of the Cmax, and thereafter a terminal half-life of 11 to 14 h accounted for the major part of the area under the concentration-time curve (AUC). During the absorption phase concentrations in saliva were even higher than those in plasma, whereas in the terminal phase a constant ratio of the concentration in saliva/concentration in plasma of between 0.5 and 1 was observed, indicating a correlation between unbound concentrations in plasma and levels in saliva (protein binding level, approximately 48%). AUC and Cmax increased proportionally to the dose over the whole range of doses investigated. Urinary excretion amounted to approximately 20% of the dose. Data on renal clearance (40 to 51 ml/min/1.73 m2) indicated partial tubular reabsorption of the drug. The pharmacokinetic parameters derived from compartmental and noncompartmental analyses were in good agreement. The kinetics could be described best by fitting the data to a two-compartment body model.     

Discriminative and participant-rated effects of methylphenidate in children diagnosed with attention deficit hyperactivity disorder (ADHD)

Despite the demonstrated beneficial effects of methylphenidate and d-amphetamine for the treatment of attention-deficit hyperactivity disorder (ADHD), the discriminative and subjective effects of these compounds in children are not well understood. This study was designed to characterize such effects in children diagnosed with ADHD. In a series of 3 experiments, 17 children were examined to determine whether methylphenidate (n = 12) and d-amphetamine (n = 5) could be reliably discriminated at doses typically used in clinical practice. Under some conditions (e.g., when they were instructed to attend to the drug effects or when a wide range of doses was used), children discriminated methylphenidate (5.0-30.0 mg) from placebo. Children tested under a range of doses of d-amphetamine (2.5-20.0 mg) were unable to discriminate this drug from placebo reliably. Neither methylphenidate nor d-amphetamine produced reliable participant-rated effects.     

Heart rate arousal and excitement in gambling: Winners versus losers.

People sometimes claim they gamble for excitement rather than money. The authors examined in a laboratory analog whether excitement is generated by the expectancy of winning money. Eighty male undergraduate students watched a videotaped horse race with an exciting neck-to-neck finish. Half bet $1 for a chance of winning $7 if they picked the winning horse; the other half predicted the winning horse without wagering. Winning and losing were experimentally manipulated. Participants with a chance to win money showed greater heart rate (HR) elevations and reported more subjective excitement while watching the race compared with those who did not wager. Of students who wagered, the winners showed higher HRs after the end of the race than did those who lost, even though differences in subjective excitement were not statistically significant. The findings suggest that the expectancy of winning money is an important contributing factor to the excitement associated with gambling. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of serotonergic manipulations on cocaine self-administration in rats

Rats were trained to self-administer cocaine (0.5 mg/kg/infusion) and were then pretreated with the 5-HT1A agonist 8-OH-DPAT (0.125, 0.25 or 0.5 mg/kg, SC). 8-OH-DPAT pretreatment produced a decrease in reinforced response rates. When the effect of 8-OH-DPAT (0.5 mg/kg, SC) on responding for a range of cocaine doses was assessed, the drug produced a decrease in response rates when lower doses of cocaine served as the reinforcer. Fluoxetine (10 mg/kg, IV), an indirect 5-HT agonist, also reduced reinforced response rates for a low dose infusion of cocaine. Rates of responding for infusions of higher cocaine doses were not affected by fluoxetine pretreatment during an FR1 schedule of reinforcement. When an FR10 schedule of reinforcement was imposed, reinforced response rates for infusions of higher doses of cocaine were also reduced. Thus, under conditions that produce high rates of responding (low dose infusion or high ratio requirements for an infusion) fluoxetine reduced responding. This effect may be due to the effects at the 5-HT1A receptor, since 8-OH-DPAT produced a similar effect on cocaine self-administration. Given that the effects of these 5-HT agonists are observed only when low doses of cocaine serve as the reinforcer or when task demands are high, it is possible that the suppression of responding reflects an effect that is not specific to the reinforcing impact of cocaine. An alternative explanation for these effects incorporates a concept of unit cost/cocaine infusion that allows for direct comparison across studies that employ different reinforcement schedules.     

Modified oral ondansetron regimen for cyclophosphamide-induced emesis in lupus nephritis

OBJECTIVE: To evaluate the antiemetic efficacy of a modified regimen of oral ondansetron and dexamethasone in patients with lupus nephritis undergoing treatment with cyclophosphamide whose conventional antiemetic regimen had failed. DESIGN: A before-after prospective observational pilot project. SETTING: A federal research hospital. PATIENTS: Fourteen outpatients with lupus nephritis receiving intravenous cyclophosphamide 0.75-1.0 g/m2 had previously experienced chemotherapy-induced emetic events (vomiting or retching) while receiving a standard combination intravenous antiemetic regimen. The regimen consisted of four doses of thiethylperazine 10 mg and diphenhydramine 25 mg every 6 hours, and two doses of lorazepam 0.5 mg every 6 hours starting at 1 hour prior to cyclophosphamide. A subset of 8 patients previously completed a blinded study in which they received the intravenous formulation of ondansetron (4 doses of 4-16 mg q4h) administered orally beginning 30 minutes prior to the cyclophosphamide infusion. MAIN OUTCOME MEASURES: The number of emetic events and cost of drug administration were assessed for the modified ondansetron intervention and compared with those of the standard antiemetic regimen. The incidence of emetic events and visual analog nausea scores for the subset of eight patients were also evaluated. INTERVENTIONS: To account for the delayed onset of emesis associated with cyclophosphamide, patients received both ondansetron 8 mg orally every 4 hours (3 doses) and dexamethasone 10 mg orally (1 dose) beginning 4 hours after the cyclophosphamide infusion. This is different from the manufacturer's recommended dose schedule, in which ondansetron is administered prior to chemotherapy. RESULTS: No emetic events were observed following the administration of oral ondansetron/dexamethasone. The 95% confidence interval for the true rate of emesis was 0% to 19.3%. There was a significant difference in efficacy between ondansetron/dexamethasone and the triple antiemetic regimen (p < 0.0002). None of the patients experienced adverse effects while receiving the ondansetron/dexamethasone regimen. Cost comparisons (including admixture and nursing administration times) for standard combination therapy and oral ondansetron/dexamethasone were $109.09 and $70.24, respectively. No difference in emetic events or nausea ratings was observed between oral ondansetron/dexamethasone tablets and oral administration of ondansetron using the intravenous formula. CONCLUSIONS: This study suggests that a modified oral ondansetron/dexamethasone regimen is safe and efficacious, and costs less than alternative regimens to prevent cyclophosphamide-induced emesis in patients with lupus nephritis.     

Effects of naltrexone on response to intravenous cocaine, hydromorphone and their combination in humans

This study evaluated the effects of i.v. cocaine, hydromorphone and their combination, and assessed the ability of oral naltrexone, an opioid antagonist, to modulate these effects. Volunteers with cocaine and heroin abuse histories (n = 8) participated in this placebo-controlled, cross-over study while residing on a closed research unit. Daily treatment with capsules containing placebo or naltrexone in ascending doses (3.125, 12.5, 50 and 200 mg) were given for 7-day periods. In thrice weekly experimental sessions, cocaine, hydromorphone and their combination were given in random order. Drug doses were given in an ascending order 1 hr apart as follows: cocaine at 0,20 and 40 mg, hydromorphone at 0, 1.5 and 3.0 mg, and the combination of 0 and 0 mg, 20 mg cocaine and 1.5 mg hydromorphone and 40 mg cocaine and 3.0 mg hydromorphone. Hydromorphone and cocaine produced distinct pharmacodynamic profiles, and the combination produced effects similar to both drugs. In some cases, the magnitude of effects produced by the combination was greater than that produced by either drug alone. Naltrexone produced dose-related blockade of hydromorphone effects, but did not after any of the physiological or subjective effects of cocaine. All naltrexone doses partially attenuated the effects of the combination and this appeared to be attributable to selective opioid blockade. These data do not support the use of naltrexone as a treatment for cocaine abuse, but suggest it may be useful for treating patients with concurrent cocaine and heroin abuse.     

Effects of oral cocaine on intravenous cocaine discrimination in humans.

This study was designed to evaluate the drug discrimination paradigm as a model for assessing the ability of potential agonist medications to block the effects of intravenous cocaine. Previous research has demonstrated that oral cocaine attenuated the subjective and physiological effects of intravenous cocaine injections, and in the absence of a known efficacious medication for cocaine use disorders, a proof-of-concept approach was used in which cocaine was acutely administered orally to block intravenous cocaine's discriminative-stimulus effects. During training, 11 cocaine-dependent participants were able to discriminate between intravenous saline and 20 mg/70 kg iv cocaine, and 8 of these participants completed the study. After training, participants ingested capsules containing either placebo or 300 mg/70 kg cocaine 60 min prior to the intravenous injection of different doses of cocaine during test sessions with no contingencies in place. Each cocaine dose was administered twice, once under each oral pretreatment condition. Training sessions were interspersed among the test sessions. Physiological and subjective effects were measured throughout each session. Oral cocaine moderately increased some of the subjective and physiological effects of the lower doses of intravenous cocaine, whereas effects at the higher doses were unaltered. Similar changes were seen for the discrimination results. Thus, although oral cocaine given acutely likely is not a viable treatment medication for cocaine dependence, the usefulness of the drug discrimination model in the evaluation of agonist treatment medications remains unclear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Zolpidem is differentiated from triazolam in humans using a three-response drug discrimination procedure

The discriminative stimulus effects of the imidazopyridine hypnotic zolpidem and the classic benzodiazepine hypnotic triazolam were examined in seven healthy volunteers using a three-response drug discrimination procedure and a within-subject design. During an initial sampling phase, the training drug conditions (placebo, 20 mg/70 kg zolpidem, and 0.5 mg/70 kg triazolam) were identified to subjects by letter codes before oral drug administration. During a subsequent training phase, subjects earned money for correct drug identifications made 3.75 h after drug administration. Five out of seven subjects acquired the three-response discrimination. Analyses of standardized and unstructured self-report questionnaires revealed that zolpidem and triazolam produced different profiles of effects; zolpidem was associated with a number of negative somatic symptoms including nausea, blurred vision, visual images/hallucinations, and heavy limbs, whereas triazolam was associated with greater sedative effects. These results demonstrate a distinct profile of discriminative stimulus and subjective effects for zolpidem, relative to triazolam, which is consistent with its somewhat distinct pharmacological profile, and provide evidence for the sensitivity of the three-response drug discrimination procedure for detecting between-drug differences.     

Discriminative-stimulus effects of zolpidem, triazolam, pentobarbital, and caffeine in zolpidem-trained humans.

Six non-drug-abusing humans were trained to discriminate 15 mg zolpidem in the present experiment. After participants acquired discrimination, a range of doses of zolpidem (2.5–15.0 mg), triazolam (0.0625–0.3750 mg), pentobarbital (25–150 mg), caffeine (100–600 mg), and placebo were tested to determine whether they shared discriminative-stimulus effects with 15 mg zolpidem. The participant-rated and performance-impairing effects of zolpidem, triazolam, pentobarbital, and caffeine were assessed concurrently. Triazolam and pentobarbital dose dependently increased zolpidem-appropriate responding. Caffeine occasioned low levels of zolpidem-appropriate responding. Zolpidem, triazolam, and pentobarbital, but not caffeine, generally produced a similar constellation of participant-rated drug effects (e.g., increased scores for the Pentobarbital, Chlorpromazine, and Alcohol Group subscale on the Addiction Research Center Inventory) and dose dependently impaired performance. These results suggest that humans can reliably discriminate zolpidem. Despite its unique benzodiazepine-receptor binding profile, the discriminative-stimulus, participant-rated, and performance-impairing effects of zolpidem are similar to those of the barbiturates and benzodiazepines. (PsycINFO Database Record (c) 2010 APA, all rights reserved)