Chapter

An International Convention on the Control of Psychotropic Substances

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Abstract

The “Convention on Psychotropic Substances, 1971” (in the following designated as “the Convention”) was initiated by the United Nations’ Commission on Narcotic Drugs, a functional commission of the Economic and Social Council, and the Expert Committee on Drug Dependence of the World Health Organization (WHO) because of the legal difficulty in controlling drugs other than those of the morphine, cocaine or cannabis type under the existing international conventions on narcotics control.

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The present investigation sought to determine whether the stimulus properties of morphine and lysergic acid diethylamide (LSD) would generalize to several narcotic analgesics which vary in their subjective effects. Morphine and saline served as discriminative stimuli for one group of rats in a 2-lever discrimination task. LSD and saline were discriminative stimuli for a second group. Depression of one lever in an operant chamber resulted in reinforcement following the administration of morphine or LSD and the opposite lever was reinforced after saline. After discriminated responding was stable, stimulus generalization tests with narcotic analgesics and antagonists showed that the stimulus properties of morphine generalized to methadone and meperidine, and partially to pentazocine, all of which produce morphine-like subjective effects in humans. Morphine stimulus properties did not generalize to nalorphine or cyclazocine, which produce dissimilar subjective effects. The stimulus properties of LSD generalized partially to cyclazocine, but not to nalorphine. In humans cyclazocine and nalorphine produce a high incidence of psychotomimetic effects, but the subjective effects of cyclazocine are differentiable from those of LSD.
Article
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1. A fixed interval-fixed ratio chain of behavior was maintained for periods as long as 6 months by intravenously administered morphine. 2. The morphine reinforced FI-FR chain was found to be a sensitive and reliable index of motivational changes induced by drug deprivation, nalorphine antagonism and pretreatment with morphine. 3. Profound behavioral disruption occurred in both shock avoidance and food reinforced ratio behavior under conditions of drug deprivation. 4. The behavioral disruption of the food reinforced and shock avoidance behaviors was ameliorated by a single self-administration of morphine. Substitution of saline for the morphine solution produced a transitory placebo effect characterized by an immediate return of the food and avoidance behaviors to their pre-deprivation baseline conditions, but followed by progressive disruption as time without the drug increased.
Chapter
A number of animal species, including man, will perform operant responses for intravenous injections of various psychoactive drugs. The comparability between certain aspects of infrahuman drug self-administration and human drug abuse (see Schuster and Thompson, 1969; Schuster and Johanson, 1974 for reviews) has validated the use of laboratory animals as a means of studying elements of human drugtaking behavior under highly controlled conditions. One of the problems with research in this area has been that, in addition to reinforcing behavior which precede them, drug injections can also affect subsequent responding. For example, an injection of cocaine will reinforce the response which produced it but may also increase the likelihood of responding over the next few minutes because cocaine often increases response rates when given noncontingently. An important area of current research concerns the development of new dependent variables that can separate the reinforcing effects of drugs from their other behavioral effects.
Chapter
In this chapter we will review existing literature on the discriminative stimulus properties of several drugs which are often classified as hallucinogens. At the same time we ‘will try to answer several questions about the usefulness of this procedure. For example, can it be used as a specific behavioral assay or screening technique for hallucinogens? Can the mechanism of action of hallucinogenic drugs be effectively studied and, if so, can it tell us anything about the nature of hallucinations?
A nasal catheter was implanted in a monkey which was restrained chronically in a specially designed cage by a freejointed metal arm and harness. Vapors of chloroform, ether or lacquer thinner were sent to the nasal cavity of the monkey through the catheter for a preset time period when he pressed a lever switch which was located on a wall of the cage. Thus, the monkey was able to inhale the organic solvents voluntarily.All six monkeys, two to each agent, took highly concentrated successive doses of the vapors during the daytime and manifested such overt signs of pharmacological effects as ataxia, mydriasis and salivation. Frequent light anesthesia was observed with chloroform. In the course of induction of or recovery from chloroform anesthesia, extreme excitation and hallucinatory behavior were occasionally observed. Two monkeys on chloroform died from suffocation when they were voluntarily self-anesthetized.
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1. Der zeitliche Verlauf der Entwicklung maximaler Abhängigkeit von Natriumbarbital bei Hunden wird beschrieben. 2. Eine Methode der Beurteilung des Schweregrades von Abstinenzerscheinungen wird dargelegt. 3. Ein Verfahren zur raschen Bestimmung der Potenz sedativ-hypnotisch wirksamer Pharmaka zur Erzeugung einer barbituratähnlichen physiologischen Abhängigkeit wird angegeben. Nachteile der Methode werden erörtert.
Article
Cocaine, methylphenidate and secobarbital were compared on a drug maintained progressive-ratio procedure in baboon subjects. Trials, scheduled throughout the day, occurred at a minimum interval of 3 hrs after completion of the preceding trial. A ratio response requirement on the initiate lever was required during each trial which terminated in a single intravenous infusion of drug. A drug was introduced on the progressive-ratio procedure with a low ratio requirement in order to obtain a baseline performance of a high stable frequency of trial completion. The ratio requirement was systematically increased every 7 days until the breaking point when the rate of completing trials fell below a criterion level. Within-subject comparison revealed that cocaine produced higher breaking points than methylphenidate at the same absolute dose, 0.4 mg/kg. At the range of doses studied, manipulation of doses of methylphenidate (0.1–0.8 mg/kg) and cocaine (0.4–1.6 mg/kg) had little effect on breaking point. In contrast, increasing doses of secobarbital (6.0 and 12.0 mg/kg) produce higher breaking points within the same subjects.
Article
A procedure for studying intravenous drug self-administration in the cat is described. Ten cats were given 24-h access to methamphetamine reinforcement (0.04 mg/kg/inj.). The subjects maintained a significantly higher response rate for drug reinforcement than for saline. The pattern of self-administration over days alternated between periods of high and low drug intake. Six additional cats were used to study the effect of dose per injection on methamphetamine self-administration under conditions of limited access. When methamphetamine was substituted at various doses per infusion in animals maintained on cocaine reinforcement, response rate was shown to be an inverted U-shaped function of dose. These studies demonstrate that methamphetamine is a reinforcer in the cat and its patterns of intake under conditions of 24-h and limited access resemble other species.
Article
Fentanyl is reported to produce a discriminative stimulus that can control food-reinforced lever pressing in rats. Other narcotics (i.e. dextromoramide, morphine, phenoperidine and piritramide) are found to be generalized with fentanyl injection, whereas the neuroleptic haloperidol is not. The subjectively experienced narcotic cue is effectively controlled by the experimental procedures described.
Article
Intravenous infusions of 2,5-dimethoxyamphetamine (2.4 mg/kg) and LSD (10 μg/kg) in the chronic spinal dog facilitated the flexor reflex, elicited the stepping reflex, increased respiration, produced a modest pupillary dilation and raised body temperature and were approximately equieffective. Cyproheptadine (0.2 mg/kg) alone antagonized the effects of LSD and 2,5-dimethoxyamphetamine (DMA) on the stepping reflex, and both cyproheptadine and phenoxybenzamine (1.0 mg/kg) reduced the actions of LSD and DMA on respiration and pupillary diameter. In another group of chronic spinal dogs tolerant to 30 μg/kg/day of LSD, cross tolerance was present to the effects of DMA on the flexor and stepping reflexes, respiration, mydriasis, temperature and behavior. Additional evidence suggested that direct tolerance to DMA can be produced and that these animals are cross tolerant to LSD. In intact dogs DMA exerted an anorexigenic effect, but was less potent than d-amphetamine. Generally the LSD-like actions of DMA were more pronounced than its amphetamine-like qualities and some actions are indicative of a mixture of drug effects.
Article
Rhesus monkeys surgically prepared with intravenous catheters were given 23 hr daily access to injection of either cocaine, d-amphetamine, 1-amphetamine, d-methamphetamine or diethylpropion on a fixed ratio 1 schedule of reinforcement for a maximum of 30 days. Responding was maintained by all these drugs but showed both day-to-day and hour-to-hour variability. The two animals self-administering 0.2 mg/kg/infusion cocaine died in less than 5 days. All 6 animals given access to 0.05 mg/kg/infusion d-amphetamine or 0.025 mg/kg/infusion d-methamphetamine also died, but tended to survive more days than animals exposed to cocaine. Three of the 5 animals whose responding was maintained by 0.5 mg/kg/infusion diethylpropion and one of the two animals whose responding was maintained by 0.05 mg/kg/infusion 1-amphetamine survived the entire 30 days despite high rates of intake. Food intake was initially decreased, but often returned to predrug levels and was not related to level of drug intake.
Article
The ability of narcotic antagonists to produce the narcotic cue was investigated in rats trained to discriminate fentanyl (0.04 mg/kg) from solvent. The partial antagonists pentazocine, cyclazocine and nalorphine were found to possess narcotic cuing activity whereas naloxone lacked any such action at doses up to 160 mg/kg. The relationship between the present findings and the ability of these drugs to produce opiate-like subjective effects in humans is discussed. The conclusion was reached that the experimental procedure used may contribute significantly to the preclinical evaluation of drug abuse liability.
Article
The discriminative effects produced by morphine in the rat were evaluated using a two-choice, discrete trial avoidance task. Stimulus control of behavior was attained with a dose of morphine one-third to one-tenth of that used in previous studies. Morphine produced dose-related discriminative effects over a 100-fold dose range. The stimulus control produced by the discriminative effects of morphine met the following criteria for classification as a specific narcotic effect: 1) oxymorphone, levorphanol, methadone and meperidine, narcotic analgesics from diverse chemical families, also produced dose-related morphine-like discriminative effects; 2) dextrorphan and thebaine, compounds structurally related to the narcotics but lacking narcotic activity, failed to produce morphine-like discriminative effects; 3) effects were blocked by the narcotic antagonist naloxone; and 4) tolerance to the discriminative effects developed upon the repeated administration of morphine and cross-tolerance extended to methadone. The discriminative effects produced by morphine were further characterized by evaluating the capacity of prototypes of other classes of psychoactive drugs to produce morphine-like discriminative effects. Profadol and pentazocine, euphorogenic analgesics with mixed agonist and narcotic antagonist properties, produced dose-related morphine-like discriminative effects whereas cyclazocine, a dysphorogenic analgesic with mixed agonist and narcotic-antagonist properties, did not. In addition, the nonopioid psychoactive drugs d-amphetamine, pentobarbital and chlorpromazine also failed to produce morphine-like discriminative effects. Thus, morphine-like discriminative effects were produced uniquely by the narcotic analgesics and euophorogenic analgesics with mixed agonist and narcotic antagonist properties. These results suggest that the component of action of morphine that enables it to function as a discriminative stimulus in the rat is analogous to the component of action of morphine responsible for producing subjective effects in man.
Article
Psychomotor stimulants are capable of controlling discriminative responding in rats. Evidence suggests that response control is central, of a fairly specific nature, and dependent on intact dopaminergic functions.
Article
The effects of several indoleamines and phenethylamines were studied in the chronic spinal dog and compared with two standard drugs, LSD and amphetamine. In the nontolerant chronic spinal dog, their effects on a variety of physiologic and behavioral functions were measured in untreated dogs, as well as dogs treated with certain antagonists. The effects of the antagonists phenoxybenzamine and cyproheptadine on the various physiologic effects were studied for all drugs. For some idoleamines and phenethylamines, the effects of chlorpromazine and pimozide were also studied. Indoleamines and phenethylamines in the LSD-tolerant chronic spinal dog and their anorexigenic effects in the intact dog were also studied. The results of these studies indicate that psilocin, mescaline, dimethyltryptamine and tryptamine are LSD-like drugs. DOM, DOB, DMA, and TMA are predominantly LSD-like drugs but do have some amphetamine-like action. PMA and PEA are predominantly amphetamine-like drugs with some LSD-like activity. MMDA and MDA have a more complicated pharmacology showing proerties that resemble LSD and amphetamine, but they have other actions which are not shared by either LSD or amphetamine, which suggests they have yet other modes of action.
Article
In an operant procedure of lever pressing on a FR10 schedule of food reinforcement, male hooded rats were trained to respond on a lever on one side of a food cup following a desipramine (10 mg/kg) injection and to respond on a lever on the other side following a saline injection. Sixty percent of the rats learned to reliably discriminate desipramine from saline. The rate of lever pressing at this dose of desipramine was 49% of the saline response rate. No tolerance to this depressant effect was observed after 20 injections. Subjects selected the appropriate desipramine lever 91, 29 and 18% of the time following 10, 2.5 and 0 (saline) mg/kg of desipramine. Imipramine and protryptyline each produced 50% selection of the desipramine lever at a dose of 40 mg/kg. Lower doses were less effective. d-Amphetamine produced 20 and 67% desipramine lever selection at 0.64 and 1.25 mg/kg respectively.
Article
There have been many recent reports characterizing the discriminative properties of morphine and related narcotic analgesics in a variety of experimental paradigms, predominantly in the rat (see preceding chapter). It is becoming increasingly evident that a strong association exists between the discriminative properties of these drugs in animals and the qualitative nature of the subjective effects produced by these same drugs in man (Shannon and Holtzman, 1976a, b). Since the abuse potential of narcotic analgesics is largely a function of the nature of their subjective effects (see Fraser, 1968; Jasinski, 1973a), animal models for evaluating this component of drug action are of obvious importance on clinical as well as on theoretical grounds.
Article
Operant work for marihuana cigarettes or money and the effects of marihuana smoking on behavior were examined in 12 casual and 15 heavy marihuana users. Male volunteers were studied in groups of four on a clinical research ward and each subject served as his own control. A 5-day base-line period was followed by a 21-day marihuana available period and a 5-day postmarihuana control period. Subjects could earn one 1-g marihuana cigarette or 50 cents by 30 minutes of sustained performance on a simple operant task. All casual and most heavy user subjects gradually increased marihuana smoking through time. The heavy users smoked more (4.3-6 cigarettes/day) than the casual users (2-3/day). Both groups worked between 2 and 5 times as many hours per day as was necessary to earn the number of cigarettes smoked. Consequently, subjects earned and saved far more money than was spent for marihuana. The heaviest smokers worked between 6.7 and 14.4 hours/day, every day. Periods of maximal work coincided with periods of maximal smoking, i.e., between 4 P.M. and 12 midnight each day. Delayed effects of marihuana dose on points earned the following day showed a dose-related decrement in operant work output. In the heavy user group, operant performance decreased sharply 24 hours after 3 ciagrettes/day were smoked, then remained relatively stable after 3 to 8 cigarettes daily and decreased further on the few occasions when more than 8 cigarettes were smoked. In the casual user group, the largest 24-hour delayed changes in performance occurred after the smoking of between 1 and 2 and 3 and 4 marihuana cigarettes. No subject stopped operant work even when he smoked 10 or more marihuana cigarettes per day. These data do not support the hypothesis that marihuana induces an "amotivational" syndrome.
Article
In a residential hospital ward setting, either sodium pentobarbital, diazepam or ethanol was made availabe for oral ingestion to volunteer human subjects with documented histories of drug abuse. During specified portions of the day, tokens could be earned by riding an exercise bicycle and exchanged for doses of a drug. Increases in the required minimum interingestion interval from 0 to 30 minutes produced decreases in the number of ingestions of sodium pentobarbital and diazepam. In another experiment, increases in the dose per ingestion (30-90 mg of sodium pentobarbital, 2-10 mg of diazepam, or 1.86-11.14 g of ethanol) produced increases in the number of ingestions. In both experiments, the effects of the manipulated variable were similar for all of the drugs studied. The study demonstrates the feasibility of human self-administration research with the sedative drugs, sodium pentobarbital and diazepam, for which substantive experimental data have not previously been reported. In addition, the results indicate that both dose and minimum interingestion interval bear a systematic controlling relationship to the occurrence of drug self-administration behavior.
Article
A method for an economical bioassay of physical dependence on sedatives is presented. Dogs maintained on sodium pentobarbital (200 mg/kg/24 h i.v.) were given periodic graded reductions in maintenance dose, and subscales for measuring signs of abstinence were developed. Using these subscales the relative potencies compared with sodium pentobarbital were determined for sodium secobarbital (RP = 0.85) and methaqualone (RP = 0.14). Sodium thiopental and methaqualone were assayed and found to be equipotent (RP = 0.96) in reducing the signs of abstinence from sodium pentobarbital. The occurrence of convulsions, during periods of complete reduction of the maintenance drug, became less frequent the longer the dogs had been maintained on a constant dose of sodium pentobarbital.
Article
A choice procedure was developed to compare the reinforcing efficacy of drug solutions delivered via intravenous catheters to rhesus monkeys. Choices were arranged between doses of cocaine or methylphenidate and saline, different doses of the same drug and doses of both drugs. In each session, monkeys were allowed to self-inject one solution five times in the presence of a stimulus. Thirty minutes after the fifth injection, a second solution could be self-injected five times in the presence of a different stimulus. Thirty minutes later, choice trials began in which both stimuli were present and monkeys could choose one of the two solutions. Rate of responding decreased with increases in dose for both cocaine (0.05-1.5 mg/kg) and methylphenidate (0.075-0.7 mg/kg). Response rates maintained by cocaine were 2 to 3 times higher than those maintained by methylphenidate. Drug was always chosen over saline. Higher doses of cocaine were preferred to lower doses except when both were above 0.5 mg/kg, when no preference was shown. Higher doses of methylphenidate were preferred over low doses, but compared to cocaine, a greater absolute difference between dose magnitude was required to demonstrate preference. When equal doses of cocaine and methylphenidate were compared, no preference was shown. On other comparisons between the drugs, the higher dose was generally preferred regardless of the drug. The reinforcing efficacy of drugs must be considered not only in terms of response rate maintained or reinforcement schedule but also with reference to concurrently available drugs.
Article
Experimental studies of human ethanol self-administration are reviewed, and a description is provided of the procedural evolution that has oc-urred in the experimental study of the determinants of human ethanol self-administration. Human experimental models of alcoholism have been established within residential laboratories which permit chronic availability of ethanol to volunteer alcoholic subjects. Experimentation within such environments has progressed from observational and descriptive studies of experimental intoxication to studies that manipulate experimental variables so as to modify (reduce) ethanol self-administration by alcoholic subjects. To observe systematic effects of manipulated variables it has been necessary to develop sensitive baselines of ethanol self-administration. When ethanol intake has been relatively unrestricted, wide spontaneous fluctuations have made difficult the evaulation of manipulated variables. When a variety of restrictions on ethanol availability have been imposed, sensitive self-administration baselines have been established which have permitted the direct experimental assessment of some of the determinants of ethanol self-administration. Six methodological principles are suggested for enhancing the information yield of future research on the determinants of ethanol self-administration. The same general methodology is suggested for research with other varieties of drug self-administration.
Article
Key-press responding of squirrel monkeys produced intravenous injections of cocaine under two simple types of schedule. Under a fixed ratio schedule, every 30th response produced an injection; steady responding at high rates of over one per second were maintained during each fixed-ratio component. Under a fixed-interval schedule, the first response occurring after a fixed time of 5 min produced an injection; there was a pause at the start of each interval and then progressively increasing responding until cocaine was injected at the end of the interval. Both squirrel monkeys and rhesus monkeys also were studied under second-order schedules of drug injection. Under one type of second-order schedule, studies only in squirrel monkeys, completion of each fixed-interval component produced only a 2 sec light; completion of the 10th fixed-interval component produced the brief light and an intravenous injection of cocaine. Under a second type of second-order schedule, each fixed-ratio component completed during a fixed time interval (5 or 60 min) produced only a 2-sec light; the first fixed-ratio component completed after the interval of time elapsed produced the brief light and an intravenous (squirrel monkeys) or intramuscular (rhesus monkeys) injection of cocaine. Under both types of second-order schedules, repeated sequences of responding were maintained during each session and characteristic fixed-interval or fixed-ratio patterns of responding were controlled by the brief visual stimuli.
Article
Pentazocine (10 mg/kg) and saline were used as discriminative stimuli in rats. After pentazocine administration, reinforcement could be obtained contingent on pressing one particular lever (left or right) in a two-lever operant chamber. Responding on the opposite lever was reinforced only after saline injections; a drug-lever combination was always held constant for each animal. Discriminated choice responding between pentazocine and saline was learned to an 80% correct criterion. Test injections of morphine produced dose-related responding on the pentazocine lever. Choice responding after 7.5 mg/kg of morphine was not significantly different from choice responding after 10 mg/kg of pentazocine. The discriminable ED50 values for both pentazocine and morphine were estimated from dose-response curves and when given in combination (pentazocine ED50 + morphine ED50), more drug-related responding occurred than occurred after either drug (ED50) alone. Naloxone produced saline-like responding but antagonized the stimulus properties of both pentazocine and morphine. However, the antagonism of the morphine cue by naloxone was significantly greater than the antagonism of the pentazocine cue. The results indicate that pentazocine and morphine are similar in at least one important respect suggesting that these drugs may share a common site of action.
Article
Hallucinogens have been known to man for thousands of years and scientific methods have been applied to the study of their effects since the later part of the last century. However, attempts to establish the pharmacologic mechanisms underlying the actions of these drugs have been hampered, in man, by ethical constraints on the type of experiments undertaken and, in animals, by the absence of an adequate model of hallucination. The work described here represents a preliminary attempt to test the hypothesis that those pharmacologic properties which serve to distinguish hallucinogens and nonhallucinogens in man are reflected in distinctive stimuli in infrahuman species. Operant behavior which is reinforced only in the presence of a specified stimulus soon occurs with greater frequency in the presence of the stimulus than in its absence and the behavior is then said to be under the control of the stimulus. In addition to well known sensory stimuli, it has been known for some time that a drug may serve as a discriminative stimulus. In this report, a general method is presented for the comparison of the stimulus properties of pharmacologic agents and the method is illustrated by a study of mescaline, its structural isomer, 2,3,4 trimethoxyphenylethylamine, and 3,4 dimethoxyphenylethylamine (DMPEA).
Article
Rats were trained to choose between the side compartments of a 3-chambered shock-escape apparatus according to whether they were injected (i.p.) with 4.0 mg/kg d-amphetamine or 0.9% saline. The d-amphetamine drug state acquired all the properties of a discriminative stimulus by producing interoceptive cues. Doses of 0.4 mg/kg nicotine, 7.4–29.7 mg/kg mescaline, 4.0–8.0 mg/kg fenfluramine and 0.048 mg/kg LSD failed to produce an amphetamine-like cue. However, l-amphetamine, 8.0 mg/kg, produced responses shown to be statistically similar to the 4.0 mg/kg training dose of d-amphetamine.
Article
Intravenous self-administration of morphine by dogs was studied before and during dependence on morphine, and after 1 to 6 months of enforced abstinence. In comparison to pedal response rates during a saline control period, 18 of 22 dogs studied showed decreased rates of responding for morphine during the initial 3-week exposure. Following subsequent passive establishment of dependence in 7 dogs, they self-administered morphine and maintained dependence. Following enforced abstinence for periods of 1 to 6 months the 7 dogs relapsed to self-administration of morphine when it was again made available. In contrast, additional dogs offered food or amphetamine reinforcements showed marked increases in pedal responding for these reinforcements within a few days after initial exposure. The results indicate that in post-dependent dogs that had maintained their dependence on morphine by self-administration, effects other than those experienced during the initial exposure to morphine are responsible for relapse.
Article
A method has been developed which permits monkeys to self-administer drug solutions, at will, through indwelling intravenous catheters. Psychological dependence on the effects of a drug occurs when a naive monkey voluntarily initiates and maintains self-administration of the drug. If, in addition to psychological dependence, the drug also produces psychotoxicity, either directly or upon abrupt withdrawal, it has a potential abuse liability. In the present study monkeys developed psychological dependence on morphine, codeine, cocaine, d-amphetamine, pentobarbital, ethanol, and caffeine. All of these drugs except caffeine produced psychotoxicity. Monkeys did not develop psychological dependence on nalorphine, morphine-nalorphine mixtures, chlorpromazine, mescaline or physiological saline.
Article
Rats were trained to choose between the arms of a T-maze apparatus according to whether they were injected i.p. with 0.1 mol/kg LSD or 0.9% saline. The LSD drug-state acquired the properties of a discriminative stimulus, possibly by producing interoceptive cues. Doses of 9.0 mol/kg psilocybin and 90 and 120 mol/kg mescaline produced cueing effects which were not significantly different from the cueing effect of LSD. However, d-amphetamine (14.8 and 29.6 mol/kg) did not appear to produce an LSD-like cue. These results suggest that LSD, mescaline and psilocybin, when administered in functionally equivalent doses, produce qualitatively similar interoceptive cues in the rat.
Article
Five centrally acting sympathomimetic amines, d-amphetamine, d-methamphetamine, ephedrine, phenmetrazine, and methylphenidate, were studied in man. All of these agents increased blood pressure and respiratory rate, produced similar types of subiective changes, and increased the excretion of epinephrine. With regard to these parameters, there was a high concordance between estimates of their relative potencies. The concordance between the potency estimates for the different parameters suggests, but does not prove, that these five agents share a common mode of central action. Further, if the peripheral modes of action as elucidated by animal studies are true for man, this study suggests that it is unlikely that their central actions in man are a consequence of the release of norepinephrine in the brain.
Article
An operant behavioral study on morphine addiction utilized a self-injection technique for giving intravenous injections to relatively unrestrained rats. The rate of self-injection varied inversely with the dose. Morphine was a reinforcer that produced almost immediate satiation.
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