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  • 1
    Electronic Resource
    Electronic Resource
    Self-injection of barbiturates and benzodiazepines in baboons (1981)
    Springer
    Psychopharmacology 75 (1981), S. 101-109 
    Details
    ISSN: 1432-2072
    Keywords: Drug self-administration ; Amobarbital ; Pentobarbital ; Secobarbital ; Clonazepam ; Clorazepate ; Diazepam ; Flurazepam ; Medazepam ; Midazolam ; Chlorpromazine ; Cocaine ; Baboons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Self-injection of three barbiturates, six benzodiazepines, and chlorpromazine was examined in baboons. Intravenous injections of drug were dependent upon completion of 160 lever presses (a 160-response fixed-ratio schedule). A 3-h time-out period followed each injection, permitting a maximum of eight injections per day. Prior to testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. Amobarbital, pentobarbital, and secobarbital maintained the highest levels of self-injection, which were similar to those maintained by cocaine. Clonazepam, clorazepate, diazepam, flurazepam, medazepam, and midazolam maintained relatively modest levels of self-injection, while chlorpromazine maintained only low levels, which were in the range of vehicle control. Of the six benzodiazepines, midazolam produced the highest levels of self-injection. At the highest self-injected doses, the barbiturates produced anesthesia in contrast to the benzodiazepines, which produced only sedation. None of the drugs affected food intake except for chlorpromazine, which produced dose-related decreases. The differences among the drug classes (i.e., barbiturate, benzodiazepine, phenothiazine) with respect to the maintenance of self-injection correspond well with the results of previous animal and human drug self-administration studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432169
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  • 2
    Electronic Resource
    Electronic Resource
    Relative abuse liability of diazepam and oxazepam: Behavioral and subjective dose effects (1984)
    Springer
    Psychopharmacology 84 (1984), S. 147-154 
    Details
    ISSN: 1432-2072
    Keywords: Diazepam ; Oxazepam ; Subjective effects ; Psychomotor effects ; Relative potency ; Time course ; Tolerance ; Abuse liability ; Drug abuse ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of diazepam (10–160 mg) and oxazepam (30–480 mg) were studied in volunteers with histories of drug abuse. Oral doses were administered every third day under double-blind and counterbalanced conditions. Dose-effects with area under the time-action curve data (AUC) showed diazepam to be 2.6-5.7-times more potent than oxazepam on various psychomotor, cognitive, staff-rated, and subjective measures. Comparison of relative potencies showed diazepam to be relatively more potent in producing ‘liking’ than in producing psychomotor and cognitive effects. Diazepam produced greater peak effects than oxazepam on a number of staff- and subject-rated measures, including liking. Onset of effect was more rapid and time to maximal effect was shorter (1–2 h versus 4–12 h) with diazepam than oxazepam, while time to offset of effect was similar for the two drugs. Diazepam was categorized as producing barbiturate-like subjective effects (38.3%) more frequently than was oxazepam (13.8%), while oxazepam was identified as placebo more often than diazepam. Repeated administration of 160 mg diazepam and 480 mg oxazepam showed that AUC liking was greater for diazepam than oxazepam and that tolerance to psychomotor and cognitive effects occurred with oxazepam but not diazepam. This study suggests that diazepam may have a higher abuse liability than oxazepam.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427437
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  • 3
    Electronic Resource
    Electronic Resource
    Naloxone does not affect cigarette smoking (1986)
    Springer
    Psychopharmacology 89 (1986), S. 261-264 
    Details
    ISSN: 1432-2072
    Keywords: Naloxone ; Cigarette smoking ; Drug self-administration ; Endorphins ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to provide information about the hypothesis that endogenous opioids mediate the reinforcing properties of cigarette smoking, the present study examined the effects of naloxone, an opioid antagonist, on cigarette smoking in seven normal volunteers. The study used experimental procedures that had previously been shown sensitive for detecting the effects of other drugs, (including a nicotine antagonist) on smoking. Isolated subjects smoked their regular brand of cigarettes freely in a naturalistic laboratory environment while watching television or reading. Sixty minutes before each 2 h smoking session subjects received an IM injection of naloxone HCl (0.0625, 0.25, 1.0, or 4.0 mg/kg) or placebo. Each subject received each treatment three times in a mixed order across days. Naloxone did not significantly affect any measure of cigarette smoking including number of cigarettes, number of puffs, or expired air carbon monoxide level. Naloxone did, however, produce significant dose-related increases in subject ratings of yawning, stretching, and relaxation. The results of the present study provide no support for the endogenous opioid theory of smoking reinforcement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174355
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  • 4
    Electronic Resource
    Electronic Resource
    Diazepam and triazolam self-administration in sedative abusers: concordance of subject ratings, performance and drug self-administration (1989)
    Springer
    Psychopharmacology 99 (1989), S. 309-315 
    Details
    ISSN: 1432-2072
    Keywords: Diazepam ; Drug abuse ; Triazolam ; Self-administration ; Benzodiazepines ; Memory impairment ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The reinforcing effects of diazepam (DZ), triazolam (TZ) and placebo were examined in eight male subjects with histories of sedative abuse. DZ (40 or 80 mg), TZ (1.0 or 2.0 mg) and placebo were each individually available for oral self-administration using a double-blind within-subject design. After an initial sampling exposure, subjects could self-administer a single dose of drug on each of 6 days by completing a progressively increasing bicycle riding requirement. All subjects initially self-administered DZ and TZ but a decreasing number of subjects continued to self-administer drugs on the remaining days; there was no difference between DZ and TZ in the total number of self-administrations. Placebo was self-administered only by one subject on two occasions. Performance measures showed that TZ produced greater memory impairment than DZ and that DZ produced residual psychomotor impairment on the next day. With repeated dosing, evidence of tolerance was seen for both drugs on psychomotor and memory performance and subject ratings of drug liking. A few modest correlations of drug self-administration and subject-ratings were obtained, suggesting some correspondence of subject verbal and drug self-administration behaviors, but these measures did not covary in a completely consistent manner.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00445549
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  • 5
    Electronic Resource
    Electronic Resource
    Differential generalization to pentobarbital in rats trained to discriminate lorazepam, chlordiazepoxide, diazepam, or triazolam (1989)
    Springer
    Psychopharmacology 98 (1989), S. 20-30 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Benzodiazepines ; Lorazepam ; Pentobarbital ; Triazolam
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In drug discrimination studies benzodiazepinetrained animals have typically responded on the drug lever when tested with barbiturates. In a recent study, greater specificity appeared to be shown when lorazepam was used as a training drug. The generality and limits of this finding were explored in the present set of experiments. The asymmetrical cross-generalization found in lorazepam-and pentobarbital-trained baboons was replicated in rats and was shown not to be a function of either lorazepam (0.1., 0.32, or 1.0 mg/kg) or pentobarbital (10 or 25 mg/kg) training dose (i.e., pentobarbital-trained rats responded on the drug lever in tests with lorazepam, but lorazepam-trained rats did not show comparable pentobarbital generalization). In the next experiment, groups of rats were trained to discriminate chlordiazepoxide (10 mg/kg), triazolam (0.1 mg/kg), or diazepam (1.0 mg/kg). Generalization to both lorazepam and pentobarbital was shown by these rats. Finally after daily pentobarbital administration, lorazepam-trained rats made a sufficient number of responses after high pentobarbital doses to permit extension of the range of pentobarbital doses tested. Pentobarbital generalization increased, but still did not occur in all rats and was unreliable in successive tests in the same rats. These results suggest less homogeneity in the discriminative stimulus effects of “depressant drugs” than generally has been recognized.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00442001
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of ventilated cigarette holders on cigarette smoking by humans (1980)
    Springer
    Psychopharmacology 68 (1980), S. 115-119 
    Details
    ISSN: 1432-2072
    Keywords: Cigarettes ; Cigarette holders ; Smoking ; Dose ; Tobacco ; Carbon monoxide ; Puffing ; Compensation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Heavy cigarette smokers individually attended daily 3-h test sessions which were run in specially designed cigarette smoking evaluation rooms. Subjects were required to use the cigarette holder provided, and were required to extinguish each cigarette 4 min after the first puff on the cigarette. Other than these restrictions, subjects were allowed to smoke ad libitum. The concentration of delivered tobacco product was varied from 100 to 10% across sessions by using graded commercially available ventilated cigarette holders. As concentration of tobacco product was decreased, rate of puffing and total number of puffs showed robust compensatory increases. Number of cigarettes increased only moderately in response to decreases in tobacco product concentration. There was little change in subjective ratings of strength on smoking satisfaction. Finally, expired air carbon monoxide (CO) values and cigarette butt weights were relatively stable across the four ventilation conditions. These later findings suggest that a significant degree of compensation had occurred in response to the concentration manipulations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432127
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  • 7
    Electronic Resource
    Electronic Resource
    Human progressive-ratio performance: Maintenance by pentobarbital (1983)
    Springer
    Psychopharmacology 79 (1983), S. 4-9 
    Details
    ISSN: 1432-2072
    Keywords: Pentobarbital ; Drug self-administration ; Fixed-ratio schedule ; Progressive-ratio schedule ; Reinforcing efficacy ; Button press ; Drug abusers ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Within a residential research ward, five human volunteers with histories of sedative drug abuse were exposed to progressive-ratio schedules of pentobarbital (200, 400, 600 mg) or placebo self-administration. All doses were letter-coded and administered under double-blind conditions. To obtain a single letter-coded dose, three subjects were required to press a set of buttons a specified number of times and two subjects were required to ride a stationary bicycle for a specified period of time. Only one dose could be obtained per day and the button-pressing or riding requirement for each letter-coded dose was increased over successive sessions until subjects failed to meet the progressive-ratio requirement (i.e., the subject chose not to work for the dose). Drug-effect ratings and subjective measures were taken 2 h after drug administration. Pentobarbital maintained dose-related increases in the maximum progressive-ratio requirement completed, the subject and staff ratings of drug effect, the subject ratings of drug ‘liking’, and the scores on the PCAG scale of the Addiction Research Center Inventory. The present study suggests that progressive-ratio schedules are sensitive and valid procedures for providing information about the relative reinforcing efficacy of drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00433007
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  • 8
    Electronic Resource
    Electronic Resource
    Oral self-administration of methohexital in baboons (1983)
    Springer
    Psychopharmacology 79 (1983), S. 120-125 
    Details
    ISSN: 1432-2072
    Keywords: Self-administration ; Drinking ; Methohexital ; Ethanol ; Sedative-hypnotics ; Baboons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Oral self-administration of methohexital was generated in baboons that were food-restricted but not water-deprived. Stable intake of an 8% ethanol solution (two baboons) or water (two baboons) was first established in 3-h-sessions. Increasing concentrations of methohexital (0.005–10 mg/ml) then were substituted with a return to the ethanol or water baseline condition between methohexital conditions. For one baboon in the ethanol baseline condition, drinking was initially suppressed by methohexital substitution, but increased under a food-induced drinking procedure. For all baboons, an inverted U-shaped function generally described the relation between methohexital concentration and volume consumed. Anesthetization was observed at concentrations of 1.6 mg/ml and above. In two-bottle choice tests, three baboons generally drank greater volumes of methohexital than water at concentrations of 0.8 mg/ml and above. After a methohexital-free period of 1–3 months methohexital self-administration was readily reestablished.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427797
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  • 9
    Electronic Resource
    Electronic Resource
    Effects of ethanol on cigarette smoking by volunteers without histories of alcoholism (1983)
    Springer
    Psychopharmacology 82 (1983), S. 1-5 
    Details
    ISSN: 1432-2072
    Keywords: Cigarettes ; Smoking ; Ethanol ; Alcoholics ; Humans ; Subjective drug effects ; Psychometrics ; Behavioral pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of ethanol on cigarette smoking were assessed in volunteer research subjects who had histories of light to moderate social drinking. Five subjects participated individually in daily 90-min sessions that were conducted in rooms equipped to permit automatic monitoring of cigarette smoking behavior. Each subject was tested at four dose levels of ethanol and placebo, which were given orally on a double-blind basis, 30 min prior to sessions. Dose order was according to a random block sequence in which each dose was given in each of five blocks of five sessions. Data from five alcoholic subjects who were similarly tested at only one ethanol dose level were used for comparison. For the nonalcoholic group, ethanol doses that produced reliable changes in group scores on various psychometric instruments produced no significant change in smoking behavior. there were differences among the nonalcoholic subjects, however, in that smoking was significantly decreased by ethanol in two subjects, was increased by ethanol in two subjects, and was unchanged in the fifth subject. For the alcoholic group, ethanol produced reliable changes in psychometric measures and significant increases in cigarette smoking. Within- and between-group analyses of results suggest that the effect of ethanol on cigarette smoking may be related to prior history of alcoholic beverage consumption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00426371
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  • 10
    Electronic Resource
    Electronic Resource
    Caffeine physical dependence: a review of human and laboratory animal studies (1988)
    Springer
    Psychopharmacology 94 (1988), S. 437-451 
    Details
    ISSN: 1432-2072
    Keywords: Caffeine ; Caffeinism ; Coffee ; Tea ; Physical dependence ; Withdrawal ; Reinforcer ; Drug self-administration ; Subjective effects ; Drug dependence ; Drug abuse ; Humans ; Animals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although caffeine is the most widely used behaviorally active drug in the world, caffeine physical dependence has been poorly characterized in laboratory animals and only moderately well characterized in humans. In humans, a review of 37 clinical reports and experimental studies dating back to 1833 shows that headache and fatigue are the most frequent withdrawal symptoms, with a wide variety of other signs and symptoms occurring at lower frequency (e.g. anxiety, impaired psychomotor performance, nausea/vomiting and craving). When caffeine withdrawal occurs, severity can vary from mild to extreme (i.e. incapacitating). The withdrawal syndrome has an onset at 12–24 h, peak at 20–48 h, and duration of about 1 week. The pharmacological specificity of caffeine withdrawal has been established. The proportion of heavy caffeine users who will experience withdrawal symptoms has been estimated from experimental studies to range from 25% to 100%. Withdrawal symptoms have been documented after relatively short-term exposure to high doses of caffeine (i.e. 6–15 days of ≥600 mg/day). Although animal and human studies suggest that physical dependence may potentiate the reinforcing effects of caffeine, human studies also demonstrate that a history of substantial caffeine intake is not a necessary condition for caffeine to function as a reinforcer. The similarities and differences between caffeine and classic drugs of abuse are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00212836
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