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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↗

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↗

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↗

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↗

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↗

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↗

Blocked and test-stimulus exposure effects in perceptual learning re-examined.

Three experiments re-examined the effects of blocked or alternated exposure to the conditioning and test stimuli and the effect of simple exposure to the test stimulus, on stimulus generalization. In all experiments rats received conditioning where a compound flavor, AX, was paired with LiCl-induced illness. All rats were tested for generalization with another flavor, BX. In Experiment 1, rats that received alternating exposure to the two flavor compounds, AX and BX, prior to conditioning showed less generalization to BX than rats that received no exposure. Exposure to BX or AX alone was also somewhat effective in reducing generalization. In Experiment 2 blocked exposure to AX and BX prior to conditioning was effective in reducing generalization, as was alternated exposure, and extended exposure to BX was more effective than the other procedures. In Experiment 3, exposure to X alone prior to conditioning produced generalization equal to that produced by alternated or blocked exposure and replicated the effect of extended exposure to BX found in the previous experiment. The relevance of the results to the theories proposed by McLaren and Macintosh [Anim. Learn. Behav. 28 (2000) 211] and Hall [Q. J. Exp. Psychol. B 56 (2003) 43] is discussed.

Animals↗

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↗

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↗

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↗

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↗

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↗

Perceptual characteristics of the amiloride-suppressed sodium chloride taste response in the rat.

The contribution of amiloride-sensitive membrane components to the perception of NaCl taste was assessed by using a conditioned taste aversion procedure. Eight independent groups of adult rats were conditioned to avoid either 0.1M NaCl, 0.5M NaCl; 0.1M NH4Cl, or 1.0M sucrose while their tongues were exposed either to water or to the sodium transport blocker amiloride hydrochloride. In contrast to rats exposed to water during conditioning, rats exposed to amiloride were unable to acquire a conditioned taste aversion to 0.1M NaCl. Differences in the acquisition of taste aversions between the amiloride- and nonamiloride-treated groups were not apparent when the conditioned stimulus (CS) was 0.5M NaCl, 0.1M NH4Cl, or 1.0M sucrose. Although the magnitude of the 0.5M NaCl aversion was similar between amiloride- and non-amiloride-treated rats, the perceptual characteristics of the CS differed between groups. Analyses of stimulus generalization gradients revealed that amiloride-treated rats generally avoided all monochloride salts after conditioning to 0.5M NaCl but not nonsodium salts or nonsalt stimuli. In contrast, rats not treated with amiloride only generalized the 0.5M NaCl aversion to sodium salts. No differences in generalization gradients occurred between groups when the CS was 0.1M NH4Cl or 1.0M sucrose. These findings suggest that the "salty" taste of NaCl is primarily related to the amiloride-sensitive portion of the functional taste response in rats. Conversely, the portion of the NaCl response insensitive to amiloride appears to have "sour-salty" perceptual characteristics and does not appear to be perceived as being salty.

Amiloride↗

Colour categorization by domestic chicks.

Spectral stimuli form a physical continuum, which humans divide into discrete non-overlapping regions or categories that are designated by colour names. Little is known about whether non-verbal animals form categories on stimulus continua, but work in psychology and artificial intelligence provides models for stimulus generalization and categorization. We compare predictions of such models to the way poultry chicks (Gallus gallus) generalize to novel stimuli following appetitive training to either one or two colours. If the two training colours are (to human eyes) red and greenish-yellow or green and blue, chicks prefer intermediates, i.e. orange rather than red or yellow and turquoise rather than green or blue. The level of preference for intermediate colours implies that the chicks interpolate between the training stimuli. However, they do not extrapolate beyond the limits set by the training stimuli, at least for red and yellow training colours. Similarly, chicks trained to red and blue generalize to purple, but they do not generalize across grey after training to the complementary colours yellow and blue. These results are consistent with a modified version of a Bayesian model of generalization from multiple examples that was proposed by Shepard and show similarities to human colour categorization.

Animals↗

The mechanisms underlying attributive projection.

The experiment investigated the validity of the cognitive dissonance reduction and stimulus generalization explanations of attributive projection. Subjects in a high dissonance condition were informed that they possessed considerable hostility (a negative trait), while those in a low dissonance condition were told that they possessed a great deal of assertiveness (a desirable trait). The dissonance mechanism received support in that (a) subjects' reports of their anxiety indicated that an ego threat was produced only in the high dissonance condition, as expected; and (b) hostility was projected onto others to a significantly greater degree than was assertiveness. The existence of only a weak relationship between degree of ego threat produced by the personality feedback and subsequent amount of projection, however, throws into question the validity of the hypothesized defensive function of projection. No support for the generalization mechanism was obtained since the subjects did not project a greater amount of either trait onto the similar targets (college students) than onto the relatively dissimilar targets (middle-aged lawyers); possible reasons for this negative result were discussed, as well as suggestions for future research.

Anxiety↗

Habituation of swimming activity in the medicinal leech.

Tactile stimulation (light stroking) of a body wall flap attached to the ventral nerve cord of the medicinal leech evokes episodes of swimming activity. This swimming response undergoes habituation, involving changes in swim initiation and swim maintenance. Repeated stimulation of the body wall flap evoked swimming activity between three and 39 times before this response failed. During repetitive stimulation, the length of swim episodes decreased by about 50%. The number of swim episodes which could be elicited was not correlated with swim episode length. Following habituation, swim initiation showed significant spontaneous recovery, but swim episode length returned only to 60% of control values. In preparations where spontaneous recovery was followed by rehabituation, the number of swim episodes elicited declined with each habituation-recovery sequence. Additional stimulation immediately following habituation trials had a dual effect: recovery of the swimming response was delayed, but the lengths of swim episodes following spontaneous recovery were increased. Pinching the body wall flap immediately restored the swimming response in an habituated preparation. Swim initiation habituated more rapidly during stimulation of anterior body wall flaps than during stimulation of mid-body or posterior flaps. However, swim length was independent of this regional variation in swim responsiveness. The number of swim episodes elicited by stimulation of body wall flaps attached to posterior or anterior segments depended upon whether this segment was stimulated before or after other flaps. In contrast, in mid-body segments there was no evidence for such stimulus generalization. The lengths of swim episodes elicited during sequential stimulation of several body wall flaps were independent of the stimulation sequence. We propose that separate processes control swim initiation and swim maintenance. These processes must be repeated in most, if not all, of the segmental ganglia of the leech ventral nerve cord.

Action Potentials↗

Generalization of cross-modal stimulus equivalence classes: operant processes as components in human category formation.

This study employed a stimulus-class rating procedure to explore whether stimulus equivalence and stimulus generalization can combine to promote the formation of open-ended categories incorporating cross-modal stimuli. A pretest of simple auditory discrimination indicated that subjects (college students) could discriminate among a range of tones used in the main study. Before beginning the main study, 10 subjects learned to use a rating procedure for categorizing sets of stimuli as class consistent or class inconsistent. After completing conditional discrimination training with new stimuli (shapes and tones), the subjects demonstrated the formation of cross-modal equivalence classes. Subsequently, the class-inclusion rating procedure was reinstituted, this time with cross-modal sets of stimuli drawn from the equivalence classes. On some occasions, the tones of the equivalence classes were replaced by novel tones. The probability that these novel sets would be rated as class consistent was generally a function of the auditory distance between the novel tone and the tone that was explicitly included in the equivalence class. These data extend prior work on generalization of equivalence classes, and support the role of operant processes in human category formation.

Acoustic Stimulation↗

The pigeon's discrimination of visual entropy: a logarithmic function.

We taught 8 pigeons to discriminate 16-icon arrays that differed in their visual variability or "entropy" to see whether the relationship between entropy and discriminative behavior is linear (in which equivalent differences in entropy should produce equivalent changes in behavior) or logarithmic (in which higher entropy values should be less discriminable from one another than lower entropy values). Pigeons received a go/no-go task in which the lower entropy arrays were reinforced for one group and the higher entropy arrays were reinforced for a second group. The superior discrimination of the second group was predicted by a theoretical analysis in which excitatory and inhibitory stimulus generalization gradients fall along a logarithmic, but not a linear scale. Reanalysis of previously published data also yielded results consistent with a logarithmic relationship between entropy and discriminative behavior.

Animals↗