摘要:

Two experiments demonstrated the efficiency of assessing drug reinforcement in humans by using a novel multiple-choice procedure. The distinguishing characteristic of the procedure is that it arranges intermittent reinforcement for choices between pairs of potential reinforcers. The procedure has three key operations: (1) a subject is exposed to the potential reinforcers; (2) a subject then makes two or more choices on a questionnaire; for each choice, the subject is required to choose one of two potential reinforcers (e.g. drug vs. drug choices and/or drug vs. money choices); and (3) subsequently only one of the choices, randomly selected, is reinforced. In the present experiments, two variations of the multiple-choice procedure were evaluated in twelve male drug abusers. Both experiments assessed the reinforcing effects of three drug conditions (200 and 400 mg/70 kg pentobarbital and placebo) which were presented no more often than every other day. The experiments demonstrated dose-related choice of pentobarbital over money as well as choice of a higher dose of pentobarbital over a lower dose or placebo. Orderly data were generated with a single-session exposure to each drug condition. Multiple-choice procedures should have applicability, not only to the investigation of drug reinforcement, but also to the study of non-drug reinforcement in humans.

ISSN:0955-8810    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The effects of the neuroleptics haloperidol,cis-flupenthixol and chlorpromazine, and the selective dopamine (DA) receptor antagonists raclopride and SCH 23390, were assessed in a conditioned reaction time task. In this operant task, rats were required to hold down a lever for a randomly determined hold duration (0.5–2.0 s) and to release the lever within 1 s of a light cue to ‘obtain food reinforcement. All drugs dose-dependently reduced the total number of lever presses and the number of rewarded responses, and all but chlorpromazine produced an abrupt cessation of responding before the end of the experimental session. However, there were variations in the ability of these drugs to impair lever release performance. Chlorpromazine and the selective D2 antagonist raclopride significantly elevated rewarded and total reaction times. The former drug also increased the number of delayed responses (i.e. those occurring with a latency of greater than I s) and reduced the percentage of rewarded responses occurring following light onset (percentage success), whilst raclopride also increased delayed reaction times. Haloperidol failed significantly to influence rewarded and total reaction times, as well as the percentage success measure. However, the lowest dose of haloperidol increased the number of delayed responses, indicating a subtle impairment of lever release performance.cis-Flupenthixol and the selective DI antagonist SCH 23390 failed significantly to influence any aspect of lever release performance. Only haloperidol andcis-flupenthixol increased the time rats took to move from the lever to the food hopper, whilst all drugs increased the time taken to return to the lever. Although feeding animals prior to the experimental session, or removing food pellets from the dispensers during the session, reduced overall response levels, the former did not influence any reaction time measure, whilst extinction only reduced percentage success. The present findings reveal that certain DA receptor antagonists impair conditioned lever release performance. However, this reaction time deficit is not obtained with all DA receptor antagonists, despite their consistent effects on other aspects of performance in the task.

ISSN:0955-8810    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

This study showed that normal social drinkers were more likely to consume ethanol after receiving a priming (preload) dose of ethanol. Twenty-eight non-problem drinkers (average consumption 9 drinks/week) participated in a six-session, double-blind choice procedure. On the first two sessions they sampled beverages containing ethanol (0.8 g/kg) or placebo (mix alone), between which they would choose on subsequent choice sessions. On the third session (dummy choice session) subjects were first asked to indicate verbally which beverage they preferred. If they chose the ethanol-containing beverage the experimenter negotiated with each subject to determine the minimum amount of money (from 1 to 30) needed to switch his or her choice from ethanol to placebo. Once this amount was determined it remained fixed for the subsequent three preload/choice sessions. Thus, on choice sessions subjects chose between the beverage which contained ethanol, and placebo plus the amount of money established in Session 3. On the preload/choice test sessions (Sessions 4–6) subjects received preloads of ethanol (0, 0.25 or 0.5 g/kg) 1 h before being given the choice between the sampled ethanol beverage and the placebo beverage plus money. The frequency of ethanol choice was the primary dependent variable. Subjective drug effects, including ratings of desire for the sampled substances, were also measured. Twenty subjects initially chose ethanol on Session 3 and switched their choice with a monetary incentive. Of these 20 subjects, four chose ethanol after the placebo preload, seven chose ethanol after the low-dose ethanol preload, and 11 chose ethanol after the higher ethanol preload (significant linear trend, Mantel-Haenszel testp> 0.03). Ratings of desire for the ethanol-containing beverage increased after the higher preload. These results suggest that ingestion of a moderate dose of ethanol increases the tendency to continue drinking, even among normal social drinkers.

ISSN:0955-8810    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

This study investigated the effects of introducing random reinforcement training after a drug discrimination between 3.0 and 15.0 mg/kg chlordiazepoxide had been acquired in rats; a two-lever food-rewarded operant procedure was used. Matched on the basis of dose-generalization test data, two dose-equiisensitive groups were formed ( A and B). Group A received 30 daily saline injections, which were followed by a random reinforcement session during which either left or right lever presses were reinforced on a probabilistic basis on each of the trials comprising a session. Group B received saline but no training or testing during this period. Subsequent testing revealed that responding conditioned to the low-dose training condition, but not to the high-dose training condition, was significantly changed in Group A. The randon reinforcement data further suggested that Group A did not discriminate saline from the low training dose. In Experiment 2, Group B of Experiment 1 was submitted to 30 random reinforcement training sessions, each preceded by a high training dose administration. Data showed that responding to the high dose, but not the low dose, was changed. For both experiments, chlordiazepoxide dose generalization following reacquisition was similar to that obtained before the random reinforcement phase. The findings indicate that the response pattern changed only for the stimulus condition present during random reinforcement. The random reinforcement manipulation did not disrupt the original discrimination between the high- and low-dose conditions.

ISSN:0955-8810    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The behaviour of rats in a novel environment was studied using a rapid time-sampling observation procedure followed by a principal component analysis (PCA ) of the data. This approach revealed that novel environment behaviour can be described by two factors or principal components. The first factor comprised rearing, sniffing-up, ambulation and locomotion (photocell counts), and was termed Escape. The second factor, which had high positive loadings of sniffing-down and locomotion and a high negative loading of immobility, was termed Exploration. The scores of individual rats on the Escape factor predicted the stimulatory effect of acutely administered d-amphetamine (1.5 mg/kg) on unconditioned behaviour. Escape high responders (HRs) showed more behavioural stimulation than Escape low responders (LRs). However, the locomotor stimulatory response of both groups increased after long-term, periodic administration ofd-amphetamine and drug discrimination training, such that the level of drug-induced locomotor activity was now equivalent for the two groups. The same rats were tested twice with various doses of d-amphetamine after being trained to discriminate this drug (0.5 mg/kg) from saline.Escape HRs were less sensitive than Escape LRs to the discriminative effects of 0.125–0.25 mg/kg d-amphetamine. In contrast to these findings, Exploration HRs and LRs were not different on any of the dependent measures described above. These results are discussed in relation to the possibility that Escape factor scores are an indication of an animal's responsivity to novelty-induced stress. If this is the case, then animals which are more susceptible to the effects of novelty stress are more sensitive to the locomotor stimulating effects of acuted-amphetamine, but less sensitive to the cueing properties of low doses of this drug.

ISSN:0955-8810    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The non-competitiveN-methyl-D-aspartate (NMDA) antagonists MK-801, PCP and ketamine have recently been found to produce full drug-appropriate responding in pigeons trained to ethanol (1.5 g/kg) in a two-key operant drug discrimination procedure. In the present study, ethanol (0.56–3.2 g/kg i.g.) was administered to pigeons trained to discriminate MK-801 (0.18 mg/kg,n- 5), PCP (1.0 mg/kg,n= 4) or the competitive NMDA antagonist CGS-19755 (1.8 mg/kg,n= 4) from vehicle. Up to doses that caused large reductions in response rates, ethanol produced only vehicle-appropriate responding in the pigeons trained to PCP and only low levels of drug-appropriate responding in pigeons trained to MK-801 and CGS-19755. The present results suggest there could be asymmetric generalization between the discriminative stimulus effects of i.g. ethanol and NMDA antagonists.

ISSN:0955-8810    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Previous research has demonstrated that the effects ofd-amphetamine on punished lever pressing of squirrel monkeys are modified by an avoidance history in which lever pressing postpones shock. In the present experiment generalization of behavioral history across responses was assessed by determining the effects ofd-amphetamine and cocaine on punished lever pressing of squirrel monkeys before and after exposure to an avoidance procedure in which a chain-pulling response postponed shock. The punishment schedule consisted of a fixed-interval 5-min schedule of food delivery in which every 30 lever presses produced a 5-mA electric shock. During avoidance sessions each chain pull postponed shock delivery for 25 s; in the absence of chain pulling, shocks occurred every 5 s. Only a single response manipulandum was present in each phase. Punished lever pressing was initially unaltered or decreased byd-amphetamine and cocaine. Following the chain-pull avoidance history, however,d-amphetamine produced dose-dependent increases in the punished lever pressing of all three monkeys at several doses that formerly did not alter or reduce responding; a similar pattern of results was obtained when cocaine was administered to two of the subjects. The effects ofd-amphetamine and cocaine on punished lever pressing were subsequently determined within the context of a multiple schedule of lever-press punishment and chain-pull avoidance, with both manipulanda present simultaneously. The effects of the drugs on punished lever pressing within the multiple schedule were similar to their initial, pre-avoidance effects for the two monkeys whose responding was increased by both drugs in the preceding, post-avoidance phase. Chain pulling during the punishment component was dose-dependently increased, suggesting that chain pulling during punishment reduced the opportunity to exhibit increases in punishing lever pressing. The remaining monkey punished lever pressing was increased by both drugs within the context of the multiple schedule. This experiment demonstrates that avoidance-dependent upward shifts in the dose-response curves ofd-amphetamine and cocaine can occur when the punishment and avoidance responses differ, and that original effects can be partially restored when both responses are available simultaneously. The results suggest that generalization across responses of the effects of a critical behavioral history may be a general property of behavioral history phenomena within behavioral pharmacology. These findings underscore the generality and importance of behavioral history as a modulatory influence on the effects of abused drugs.

ISSN:0955-8810    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The involvement of monoamine neurotransmitter uptake in the discriminative stimulus effects of cocaine was examined in rats (n= 48) trained to discriminate 10 mg/kg of this substance from saline in a two-lever, water-reinforced (FR 20), drug discrimination situation. Compounds that act primarily by inhibiting dopamine (DA) uptake substituted for the cocaine cue; the order of potency was mazindol nomifensine GBR 12909 bupropion, although efficacy was lowest with GBR 12909. Desipramine, which inhibits norepinephrine (NE) uptake, substituted partially for cocaine while two drugs that inhibit serotonin (5-HT) uptake, citalopram and fluoxetine, did not mimic cocaine. When given in combination with cocaine,cis-flupenthixol and SCH 23390 reduced responding on the cocaine-appropriate lever significantly and to a greater extent than either haloperidol, ( |Mp )sulpiride or ( - ) sulpiride; neither ( + )sulpiride nor metergoline had significant effects. Cocaine substitutions with DA uptake inhibitors were also attenuated to varying extents bycis-flupenthixol, SCH 23390 and haloperidol, but not by metergoline. These data, in conjunction with results reported previously, suggest that inhibition of DA uptake is involved to a greater extent than either NE or 5-HT uptake in the discriminative stimulus properties of cocaine and related compounds. Since both the cocaine cue and its substitution by DA uptake inhibitors appear to be blocked most effectively, reliably and potently by compounds that act either non-selectively at DA receptors (cis-flupenthixol) or primarily at D1 receptors (SCH 23390), D1 mechanisms may play a particularly important role in the neuronal substrates of these behavioral effects.

ISSN:0955-8810    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

A previous experiment had shown that the benzodiazepine receptor (BZR) agonist, clonazepam, selectively increased the consumption of a 0.05|X% sodium saccharin solution without change in water intake, in a two-choice preference test. The first aim of this study was to investigate the effects of two benzodiazepine receptor partial agonists, bretazenil (Ro 16–6028) and Ro 17–1812, in the same test. The results showed that both drugs produced effects similar to those observed earlier with clonazepam. The second aim was to investigate the effects of the two compounds on consumption of a 0.005|X% quinine solution in a two-choice test. Both drugs increased the consumption of the quinine solution without alteration in water intake. In addition, in separate single-choice acceptance tests, both drugs significantly increased the consumption of a familiar, highly palatable 3|X% sucrose solution. These data are considered in relation to alternative hypotheses for BZR-mediated effects in choice tests.

ISSN:0955-8810    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0955-8810    

出版商:OVID    

年代:1993

数据来源: OVID