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Results for “Generalization, Stimulus”

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PubMed1978

Narcotic cuing and analgesic activity of narcotic analgesics: associative and dissociative characteristics.

By using a discrete-trial, two-lever, food-reinforced discrimination learning paradigm, rats were trained to discriminate the narcotic analgesic fentanyl (0.05 mg/kg) from saline. Stimulus generalization experiments with lower fentanyl doses (0.0025 to 0.02 mg/kg) were carried out to generate individual threshold doses. The latter were compared with the sensitivity of the same rats to the analgesic effect of fentanyl, and it was found that there is no correlation between these two sets of data. In a time-effect experiment, the duration of fentanyl's cuing effect was compared with that of its analgesic effect, and it was found that the time-effect characteristics of the narcotic cue are similar to those of analgesia. Again, however, there was no correlation between the duration of both effects within the same group of animals. The results further deliniate the associative and dissociative characteristics of the narcotic cue and narcotic analgesia.

Analgesics↗

PubMed1976

Conditioned suppression of an operant response using d-amphetamine as the conditioned stimulus.

The use of a drug state as a conditioned stimulus (CS) in a classical conditioning paradigm was investigated. Suppression of a single-lever food-reinforced response (variable-interval 60 s) served as an index of a classically conditioned response (conditioned suppression). d-Amphetamine (0.8 mg/kg) injections were paired with a series of inescapable shocks. Following drug-shock pairing, the effects of d-amphetamine on operant response totals was compared to effects obtained in control subjects which had received unpaired d-amphetamine and shock exposures. d-Amphetamine administered during daily operant sessions unaccompanied by shock was an effective CS for conditioned suppression of the operant response. Administration of cocaine hydrochloride (7.5 mg/kg) also produced a decrease in total responses, suggesting stimulus generalization from the shock-paired drug to a novel drug.

Animals↗

PubMed1985

Drug discrimination training with a single choice trial per session.

All drug discrimination procedures share in common the practice of providing for multiple choice opportunities per training session. This practice allows nondrug cues (presence or absence of reinforcement) to mediate choice behavior during that portion of the session following the initial choice. Investigators who have acknowledged this problem typically use only first-trial choice performance to evaluate discriminative control by the drug cue, and consider additional choice training following the delivery or nondelivery of the first reinforcer to be facilitatory in establishing drug-mediated discriminative control. In this experiment, rats were trained to discriminate 4.0 mg/kg morphine from saline in a novel procedure that employed a single choice trial per training session. Choice performance was characterized during discrimination acquisition and in subsequent stimulus generalization testing. The results indicated that when all reinforcers are made contingent on correct performance during a single choice trial, rapid and stable control of drug-mediated choice behavior, is observed. In addition, the results demonstrated that additional choice training following the delivery or nondelivery of the first reinforcer is not a necessary antecedent toward establishing drug-mediated discriminative control.

Animals↗

PubMed2001

Differential interaction of GBR 12909, a dopamine uptake inhibitor, with cocaine and methamphetamine in rats discriminating cocaine.

RATIONALE: Inhibitors of neuronal dopamine uptake, such as GBR 12909, decrease IV cocaine self-administration by laboratory animals and have been proposed as potential therapeutic agents for abuse of psychomotor stimulant drugs. OBJECTIVES: This study was performed to determine how GBR 12909 alters the discriminative stimulus effects of methamphetamine and cocaine. METHODS: Rats were trained to discriminate between IP injections of 10 mg/kg cocaine and saline and were tested for stimulus generalization to cocaine, GBR 12909, and methamphetamine. Based upon the ED50 of the individual drugs, combinations of GBR 12909 and either cocaine or methamphetamine were tested that comprised a) 1 part GBR 12909 and 2 parts cocaine or methamphetamine, or b) 2 parts GBR 12909 and 1 part cocaine or methamphetamine. RESULTS: GBR 12909 and cocaine were equipotent and 30-fold less potent than methamphetamine in producing cocaine-like discriminative effects. GBR 12909 and cocaine produced cocaine-like discriminative effects synergistically in the ratio of 1 part GBR 12909:2 parts cocaine (0.16+0.32 to 1.92+ 3.87 mg/kg) and nearly synergistically in the ratio of 2 parts GBR 12909:1 part cocaine (0.32+0.16 to 3.92+ 1.91 mg/kg). GBR 12909 and methamphetamine (0.32+0.02 to 3.20+0.22 mg/kg or 0.65+0.01 to 6.53+0.1 mg/kg) were simply additive in both sets of fixed-ratio dose combinations. CONCLUSIONS: The synergy of GBR 12909 and cocaine and the additivity of GBR 12909 and methamphetamine run counter to the presumed mechanisms of action of these drugs at dopamine nerve terminals, which might have implications for the use of GBR 12909 in the treatment of addiction to cocaine or amphetamines.

Animals↗

PubMed1982

Treatment of an abnormal avoidance of fluid consumption.

Adipsia is an uncommon, life-threatening condition which refers to an absence of thirst or an abnormal avoidance of fluid consumption. A behavioral intervention was successfully used in the treatment of severe adipsia in a multi-handicapped adolescent whose water intake was almost entirely limited to the water content of the foods he consumed. Using edible reinforcement and a set of commercial measuring utensils (from 1/4 teaspoon to 1 cup), milk consumption was established through a behavior shaping regimen. Follow-up results over 1 year indicated that the behavioral progress was maintained, problems with dehydration were eliminated, and stimulus generalization to several other fluids occurred.

Adolescent↗

PubMed1976

Cocaine cue in rats as it relates to subjective drug effects: a preliminary report.

Using a food-reinforced two-lever operant method, rats (n=5) could be trained to discriminate 10 mg/kg cocaine from saline. Stimulus generalization experiments with lower doses (0.31-5.0 mg/kg) revealed that the cocaine cue is a dose-related phenomenon. Neuroleptic drugs were found relatively ineffective as possible antagonists of the cocaine cue, and no antagonistic effect whatsoever was obtained with dibenamine, propranolol, cyproheptadine and methysergide. iamphetamine (1.25 mg/kg) and apomorphine (0.31 mg/kg) were generalized with cocaine, and a dopaminergic involvement is discussed.

Amphetamine↗

PubMed1979

In vivo evidence of partial agonist activity exerted by purported 5-hydroxytryptamine antagonists.

Using a food-reinforced two-lever operant method, rats (n = 9) were trained to discriminate 0.16 mg/kg LSD from saline. Tests for stimulus generalization in rats so trained indicated that the purported 5-HT antagonists cyproheptadine (1.25 and 10 mg/kg), methysergide (0.16 to 10 mg/kg) and mianserin (2.5 to 40 mg/kg) produced partial generalization with LSD. The hallucinogens mescaline (5 to 40 mg/kg) and quipazine (1.25 to 5 mg/kg) were also generalized with LSD. The data suggest that cyproheptadine, methysergide and mianserin may produce partial agonist effects in addition to their antagonist action at central 5-HT receptor sites.

Animals↗

PubMed1986

Persistence behavior of chronic low back pain patients in an acute pain situation.

The test behavior of 24 chronic low back pain patients was compared with the behavior of 24 healthy control Ss., matched for age and sex, in an experimental, acute pain situation (cold pressor-test). Chronic low back pain patients showed poorer persistence behavior and reported more pain. Thus, elements of typical chronic low back pain behavior were also present in an acute pain situation. These findings are discussed within the framework of stimulus-generalization theory. In addition, the effect of different coping strategies on pain tolerance was reconfirmed. The chronic low back pain group and the control group did not cope differently.

Acute Disease↗

PubMed1993

Discriminative stimulus effects of the PCP/sigma-ligand (+)-N-allylnormetazocine in monkeys.

(+)-N-Allylnormetazocine [(+)-NANM] binds to both the phencyclidine (PCP) receptor and the sigma-site in brain, with some selectivity for the latter. In rats, the discriminative stimulus effects of (+)-NANM are primarily PCP like. The present study was performed to determine if the discriminative effects of (+)-NANM in a primate species might reflect the actions of this drug at the sigma-site. Six squirrel monkeys were trained to discriminate between IM injections of saline and 1.0 mg/kg (+)-NANM in a two-choice discrete-trial avoidance procedure. In tests of stimulus generalization, dose-dependent increases in trials completed on the (+)-NANM choice lever were produced by (+)- and (-)-NANM, by PCP and the PCP-like drugs MK-801 and thienylcyclohexyl-piperidine, and by the opioids (+)- and (-)-cyclazocine and dextrorphan; order of potency correlated with reported affinities for the PCP receptor. High-affinity sigma-ligands, (+)-pentazocine, 1,3-di-ortho-tolylguanidine (DTG), haloperidol, and BMY 14802, as well as agonists at mu- and kappa-opioid receptors, occasioned selection of the saline-appropriate choice lever. Selection of the (+)-NANM choice lever was reduced by up to 35-50% when 1.0 mg/kg (+)-NANM was given concurrently with haloperidol or BMY 14802, but was not affected substantially by (-)-butaclamol, another sigma-ligand, or by naltrexone, an opioid antagonist. The discriminative effects of (+)-NANM in squirrel monkeys appear to be mediated largely by the PCP receptor and not by the sigma-site or opioid receptors.

Animals↗

PubMed1995

Methcathione ("cat"): an enantiomeric potency comparison.

With regard to its chemical structure, methcathinone is to cathinone what methamphetamine is to amphetamine. Although it is a drug of abuse outside the United States, methcathione is only recently making an appearance on the clandestine market in this country and has just been classified a Schedule I substance under the Emergency Scheduling Act. We have previously demonstrated that racemic methcathinone produces locomotor stimulation in mice, and substitutes for cocaine and (+)amphetamine in rats trained to discriminate either cocaine or (+)amphetamine, respectively, from saline in tests of stimulus generalization. Because an enantiomeric potency comparison has never been reported for the optical isomers of methcathinone, in the present investigation we synthesized samples of S(-)- and R(+)methcathinone and compared them for their ability: a) to produce locomotor stimulation in mice, b) to elicit cocaine-like responding in rats trained to discriminate 8.0 mg/kg of cocaine from saline vehicle, and c) to elicit (+)-amphetamine-appropriate responding in rats trained to discriminate 1.0 mg/kg of (+)amphetamine from saline vehicle. S(-)Methcathinone was about twice as potent as S(+)amphetamine and three to five times more potent than R(+)methcathinone in the three pharmacologic assays. We conclude that both optical isomers possess central stimulant character, but that S(-)methcathinone is somewhat more potent than R(+)methcathinone.

Animals↗

PubMed1994

Assessing spiradoline-like discriminative effects of DuP 747: influence of route of administration.

DuP 747, trans-3,4-dichloro-N-methyl-N-[2-(pyrrolidin-1-yl)-1,2,3,4- tetrahydronaphthalen-1-yl]benzeacetamide methanesfonate, is a recently synthesized analgesic drug that binds with high affinity and selectivity to the kappa-opioid receptor. In order to determine if DuP 747 has kappa-like discriminative effects it was tested for stimulus generalization in rats trained to discriminate between SC injections of saline and 3.0 mg/kg of spiradoline, a potent kappa-opioid agonist. A range of drug doses was administered by each of several routes 30 min before a test session. Spiradoline occasioned orderly dose-dependent increases in spiradoline-appropriate lever selection after SC or IP administration, with ED50s of 0.65 and 1.75 mg/kg, respectively. In contrast, DuP 747 (1.0-30 mg/kg) occasioned little spiradoline-appropriate lever selection when administered SC, but was generalized from spiradoline partially when administered IP (ED50 = 5.9 mg/kg) or PO (ED50 = 59 mg/kg). The 5-hydroxy-desmethoxy metabolite of DuP 747, administered SC (0.3-10 mg/kg), occasioned selection of the saline-appropriate lever only. That DuP 747 had little spiradoline-like activity after SC administration suggests that a metabolite of DuP 747 was responsible for the spiradoline-appropriate responding that followed IP and PO administration of the drug, apparently a metabolite other than 5-hydroxy-desmethoxy-DuP 747.

Analgesics↗

PubMed1994

Monoamine systems in the discriminative effects of spiradoline, a kappa-opioid agonist.

The results of studies on mice indicate that the antinociceptive effects of kappa-opioid agonists are due, in part, to activation of the 5-HT2 type of serotonin receptor. One objective of this study was to determine if the discriminative effects of spiradoline, a kappa-opioid agonist, are mediated by 5-HT2 receptors in rats also. A second objective was to confirm findings that dopamine receptor antagonists produce spiradoline-like discriminative effects (Ohno et al., 1992). Rats were trained to discriminate between spiradoline (3.0 mg/kg) and saline in a discrete-trial avoidance/escape procedure. In subsequent tests of stimulus generalization, the discriminative effects of spiradoline were not mimicked by fenfluramine (0.3-10 mg/kg) or fluoxetine (1.0-10 mg/kg), drugs that enhance serotonergically mediated neurotransmission, nor were they blocked by the 5-HT2 antagonists pirenperone (0.01-1.0 mg/kg) and ketanserin (0.1-10 mg/kg), or potentiated by fluoxetine pretreatment. Neither the dopamine receptor antagonists haloperidol (0.01-0.3 mg/kg) and sulpiride (3.0-100 mg/kg) nor the agonists apomorphine (0.03-0.3 mg/kg) and d-amphetamine (0.1-3.0 mg/kg) engendered spiradoline-like discriminative effects. These results demonstrate further the pharmacological specificity of the discriminative effects of spiradoline, but provide no evidence for mediation by serotonergic or dopaminergic systems.

Analgesics↗

PubMed1986

Discriminative stimulus properties of phenylisopropylamine derivatives.

The phenylisopropylamine unit is a common structural fragment amongst many centrally-acting agents. However, these agents do not necessarily produce similar behavioral effects in test subjects. For example, the phenylisopropylamine derivative amphetamine is a central nervous system (CNS) stimulant whereas its 2,5-dimethoxy-4-methyl analog, i.e. DOM, is considered to be a hallucinogen. Employing animals trained to discriminate either (+)-amphetamine or (+/-)-DOM from saline in a two-lever operant procedure, stimulus generalization studies were conducted to evaluate members of a series of methoxy-substituted, and related, phenylisopropylamines. In this manner, it was possible to classify these agents as to which produced amphetamine-like effects, and which produced DOM-like effects.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1984

Structure-activity studies on amphetamine analogs using drug discrimination methodology.

Animals (rats) trained to discriminate 1.0 mg/kg of S(+)-amphetamine sulfate from saline, using a standard operant training procedure, were administered doses of various amphetamine analogs in tests of stimulus generalization in order to study structure-activity relationships (SAR). The types of structural variation of the amphetamine molecule that were investigated included (a) benz-fusion of the aromatic nucleus, (b) alpha-demethylation of the alkyl side chain, (c) conversion of the benzylic methylene to a carbonyl group, and (d) conformational restriction of the side chain. Benz-fusion and alpha-demethylation appear to have a detrimental effect on activity in that none of these analogs produced amphetamine-appropriate responding. However, the carbonylated analog, i.e., cathinone, was found to be equipotent with amphetamine. Furthermore, as with amphetamine, the S-isomer of cathinone was found to be more active than its enantiomer. With respect to the conformationally-restricted analogs, the most potent compound was 2-aminotetralin which was about half as active as racemic amphetamine.

Alkaloids↗

PubMed1998

MDMA-like stimulus effects of hallucinogens in male Fawn-Hooded rats.

A two-lever, food-motivated, operant technique was employed to train the purportedly serotonergically dysfunctional Fawn-Hooded (FH) rat to discriminate 1.5 mg/kg MDMA. Once all 10 male subjects learned the MDMA-vehicle discrimination at criterion performance level, doses different than the training dose were used to generate a dose-response discrimination gradient. The ED50 value of MDMA was shown to be 0.136 mg/kg, not significantly different from that of previously trained Sprague-Dawley male rats. Thus, the Fawn-Hooded rat appears to not differ in its sensitivity to lower doses of MDMA. Testing for MDMA-like stimulus generalizations with other drugs indicated that the MDMA derivative MDE produced generalization at a dose of 2.25 mg/kg and allowed for an ED50 value of 0.496 mg/kg. Like MDE, the testing of alpha-ethyltryptamine was shown to produce MDMA-like responding. Lastly, a dose of 0.12 mg/kg LSD produced 90% MDMA-lever selection. In contrast to MDMA generalizations to these three drugs, testing of cocaine at doses of 2.5-10 mg/kg and mescaline at 8-14 mg/kg did not produce MDMA-like discriminative effects. The results of this testing in the presumably serotonergically dysfunctional Fawn-Hooded rat would indicate that this line not only can discriminate MDMA as well as heterogenous-bred lines, but also shows the same discriminative generalizations and nongeneralizations from MDMA to serotonergic and dopaminergic agents.

Animals↗

PubMed1986

Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class.

The alpha-ethyl phenethylamine derivative 1-(1,3-benzodioxol-5-yl)-2-butanamine was prepared. An asymmetric synthesis was used to prepare the enantiomers of this compound and the related alpha-methyl homologue (MDA). The racemates and enantiomers of both compounds were evaluated in the two-lever drug discrimination assay in rats trained to discriminate saline from 0.08 mg/kg of LSD tartrate. Stimulus generalization occurred with the racemate and the R-(-) enantiomer of the alpha-methyl homologue and the S-(+) enantiomer of the alpha-ethyl primary amine. No generalization occurred with the other enantiomers or with the N-methyl derivatives of either series. Human psychopharmacology studies revealed that the N-methyl derivative of the title compound was nonhallucinogenic and that it had a new, novel psychoactive effect. It is suggested that this compound is the prototype of a new pharmacologic class that may have value in facilitating psychotherapy and that this class be designated as entactogens.

Adult↗

PubMed2000

Displaced aggression is alive and well: a meta-analytic review.

Content analysis of 122 social psychology textbooks confirmed that displaced aggression received a surge of attention immediately following J. Dollard, L. W. Doob, N. E. Miller, O. H. Mowrer, and R. R. Sears (1939), but subsequent interest sharply declined. Contemporary texts give it little attention. By contrast, meta-analysis of the experimental literature confirms that it is a robust effect (mean effect size = +0.54). Additionally, moderator analyses showed that: (a) The more negative the setting in which the participant and target interacted, the greater the magnitude of displaced aggression; (b) in accord with N. E. Miller's (1948) stimulus generalization principle, the more similar the provocateur and target, the more displaced aggression; and (c) consistent with the contrast effect (L. Berkowitz & D. A. Knurek, 1969), the intensity of initial provocation is inversely related to the magnitude of displaced aggression.

Aggression↗

PubMed1977

Stimulus similarity as a determinant of Pavlovian conditioning.

Three experiments carried out second-order Pavlovian conditioning using either similar or dissimilar first- and second-order stimuli. Experiments 1 and 2 used rat subjects in a conditioned suppression and an appetitive conditioning preparation, respectively. Experiment 3 used pigeons in an auto-shaping procedure. All three experiments were designed to identify the effects of similarity upon conditioning as distinct from its effects upon sensitization or stimulus generalization. Each experiment found superior conditioning when similar stimuli were paired. Several theoretical implications of these findings are discussed.

Animals↗