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PubMed1969

Generalization gradients and stimulus control in delayed matching-to-sample.

Neurological patients were subjects in delayed visual matching-to-sample. The sample and choice stimuli were ellipses of varying size. By measuring the difference in size between the sample on a given trial and the ellipse the subject chose on that trial, gradients of differences between samples and choice stimuli could be plotted. These difference gradients broadened with increasing delays. Sharp gradients were controlled by the samples. Flat gradients were controlled by features of the choice display, independently of the samples. Intermediate gradients reflected combined control by the samples and by the choice displays.

Adult↗
PubMed2004

Comparison of the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) and cocaine: asymmetric generalization.

Evidence suggests that +/- 3,4-methylenedioxymethamphetamine (MDMA) and psychostimulants produce similar but non-identical stimulus effects in animals. To examine this hypothesis, groups of rats were trained to discriminate either MDMA (1.5 mg/kg) or cocaine (8 mg/kg) from saline vehicle using a two-lever operant procedure under a variable interval (VI) 15 s schedule of reinforcement. Once the animals were trained, tests of stimulus generalization were conducted with +/- MDMA, cocaine, S+ MDMA, and R- MDMA. As previously demonstrated, both S+ MDMA and R- MDMA (ED50 = 0.8 and 1.2 mg/kg, respectively) substituted for +/- MDMA. Stimulus generalization also occurred upon administration of cocaine (ED50 = 4.6 mg/kg) to the +/- MDMA-trained animals. In the cocaine-trained animals, however, stimulus generalization did not occur to +/- MDMA, S+ MDMA nor R- MDMA. Receptor binding profiles for MDMA and cocaine were compared in an effort to identify any novel and common receptor-based mechanism(s) to explain stimulus generalization of MDMA-trained animals to the effects of cocaine, but only their actions on neurotransmitter transporters seem applicable. Taken together, the results indicate that stimulus substitution between MDMA and cocaine is asymmetric and suggest that although similarities exist between the stimulus actions of MDMA and cocaine, differences might be explained by their differential effects on increasing synaptic concentrations of serotonin (5-HT), dopamine (DA), and/or norepinephrine (NE).

Animals↗
PubMed1998

American College of Sports Medicine Position Stand. The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults.

ACSM Position Stand on The Recommended Quantity and Quality of Exercise for Developing and Maintaining Cardiorespiratory and Muscular Fitness, and Flexibility in Adults. Med. Sci. Sports Exerc., Vol. 30, No. 6, pp. 975-991, 1998. The combination of frequency, intensity, and duration of chronic exercise has been found to be effective for producing a training effect. The interaction of these factors provide the overload stimulus. In general, the lower the stimulus the lower the training effect, and the greater the stimulus the greater the effect. As a result of specificity of training and the need for maintaining muscular strength and endurance, and flexibility of the major muscle groups, a well-rounded training program including aerobic and resistance training, and flexibility exercises is recommended. Although age in itself is not a limiting factor to exercise training, a more gradual approach in applying the prescription at older ages seems prudent. It has also been shown that aerobic endurance training of fewer than 2 d.wk-1, at less than 40-50% of VO2R, and for less than 10 min-1 is generally not a sufficient stimulus for developing and maintaining fitness in healthy adults. Even so, many health benefits from physical activity can be achieved at lower intensities of exercise if frequency and duration of training are increased appropriately. In this regard, physical activity can be accumulated through the day in shorter bouts of 10-min durations. In the interpretation of this position stand, it must be recognized that the recommendations should be used in the context of participant's needs, goals, and initial abilities. In this regard, a sliding scale as to the amount of time allotted and intensity of effort should be carefully gauged for the cardiorespiratory, muscular strength and endurance, and flexibility components of the program. An appropriate warm-up and cool-down period, which would include flexibility exercises, is also recommended. The important factor is to design a program for the individual to provide the proper amount of physical activity to attain maximal benefit at the lowest risk. Emphasis should be placed on factors that result in permanent lifestyle change and encourage a lifetime of physical activity.

Adult↗
PubMed2006

Generalization gradients for acquisition and extinction in human contingency learning.

Two experiments investigated the perceptual generalization of acquisition and extinction in human contingency learning. In Experiment 1, the degree of perceptual similarity between the acquisition stimulus and the generalization stimulus was manipulated over five groups. This successfully generated a generalization gradient of acquisition. In the subsequent phase, the response to the generalization stimulus was extinguished in each group. Finally, the acquisition stimulus was presented again. The response recovered differently over groups, thereby establishing the generalization gradient of extinction. In Experiment 2, the acquisition stimulus itself was extinguished before the set of generalization stimuli was tested between groups. One group evidenced a response recovery at test, which suggests that the gradient of acquisition is somewhat broader than the gradient of extinction.

Extinction, Psychological↗
PubMed1993

MDMA-like stimulus effects of alpha-ethyltryptamine and the alpha-ethyl homolog of DOM.

One-carbon homologation of phenylalkylamine or indolylalkylamine hallucinogens containing an alpha-methyl substituent typically results in a reduction of hallucinogenic potency; however, this same structural change has little to no effect on agents that produce MDMA-like effects. In the present investigation, rats trained to discriminate 1.5 mg/kg of MDMA (3,4-methylenedioxymethamphetamine) from saline vehicle were employed to determine if the alpha-ethyl homologs of the hallucinogens 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and alpha-methyltryptamine (alpha-MeT)--that is, alpha-EH DOM (BL-3912) and alpha-EtT, respectively--would produce stimulus effects similar to those of MDMA. Although the MDMA stimulus failed to generalize to DOM (previously published) and alpha-MeT (this study), MDMA stimulus generalization occurred both to alpha-EH DOM (ED50 = 1.3 mg/kg) and alpha-EtT (ED50 = 3.5 mg/kg). A (+)amphetamine stimulus (training dose = 1.0 mg/kg) only partially generalized to these two agents, suggesting that the MDMA stimulus generalization involves more than a simple amphetamine-like action. As such, this is the first demonstration that classical hallucinogens can produce MDMA-like effects upon homologation and that MDMA-like stimulus effects can be associated with an indolylalkylamine. Furthermore, these results continue to support the concept that an intact methylenedioxy ring system, such as that found in MDMA and other MDMA-related agents, is not a structural requirement for drugs to produce MDMA-like effects.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1997

Scalar timing in temporal generalization in humans with longer stimulus durations.

Three experiments investigated temporal generalization performance in humans by using stimulus durations similar to those previously used with rats. In most conditions, chronometric counting was prevented by concurrent shadowing of temporally irregular numbers. Experiment 1 examined performance with visual stimuli, when the standard was 4.0 s long and nonstandard stimuli were spaced either linearly or logarithmically around the standard. Generalization gradients were asymmetrical with linear spacing but symmetrical with logarithmic spacing, a result obtained previously with humans. Experiment 2 used auditory stimuli and varied the standard across values of 2.0, 4.0, 6.0, and 8.0 s. All gradients were asymmetrical, and good superposition was obtained, indicating conformity to scalar timing. Experiment 3 prevented or encouraged chronometric counting by changing instructions, and temporal generalization gradients differed when counting was and was not used.

Animals↗
PubMed1998

Discriminative stimulus properties of (-)ephedrine.

Ephedrine, a structural analog of methamphetamine, is one of the major constituents of legally available herbal dietary supplements. Although racemic ephedrine and ephedra extract have been previously used as training drugs in drug discrimination studies, there is evidence that the two optical isomers of ephedrine do not produce identical amphetamine-like stimulus effects in rats. Consequently, we trained a group of six male Sprague-Dawley rats to discriminate 4 mg/kg of the more potent optical isomer of ephedrine, (-)ephedrine, from saline vehicle. The (-)ephedrine stimulus (ED50 = 0.8 mg/kg) generalized to other central stimulants such as S(+)amphetamine (ED50 = 0.4 mg/kg), cocaine (ED50 = 2.7 mg/kg), methylphenidate (ED50 = 1.2 mg/kg), S(-)methcathinone (ED50 = 0.3 mg/kg), and caffeine (ED50 = 36.7 mg/kg), but stimulus generalization failed to occur to either S(+)methamphetamine or N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA). In addition, although we have previously shown that a (+)amphetamine stimulus generalizes to (-)ephedrine but not to (+)ephedrine, in the present investigation the (-)ephedrine stimulus generalized to (+)ephedrine (ED50 = 2.6 mg/kg). From the findings (a) that (-)ephedrine is approximately 10 times less potent than (+)amphetamine in (+)amphetamine-trained rats, whereas it is only half as potent as (+)amphetamine in (-)ephedrine-trained animals; (b) that the (-)ephedrine stimulus failed to generalize to (+)methamphetamine; and (c) that the (-)ephedrine stimulus generalized to (+)ephedrine, it is concluded that the stimulus effects of (+)amphetamine and (-)ephedrine as training drugs, while similar, are not identical. It is also concluded that the stimulus effects of (-)ephedrine and those of the designer drug MDMA, while perhaps sharing some amphetaminergic commonality, are nonidentical.

Animals↗
PubMed1988

Generalization of the discriminative stimulus properties of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and ipsapirone to yohimbine.

Rats were trained with either 8-OH-DPAT (0.2 mg/kg) or ipsapirone (10 mg/kg) versus saline in a 2-lever discrimination task. Tests of generalization were then conducted with yohimbine. All drugs were administered IP 15 min before testing. In 8-OH-DPAT-trained subjects, 85% of the responses following yohimbine (3 mg/kg) were on the drug-appropriate lever. Likewise, yohimbine (6 mg/kg) yielded 86% drug-appropriate responses in ipsapirone-trained rats. Previous studies have provided evidence that both 8-OH-DPAT and ipsapirone have high affinity for 5-HT1A receptors and the anxiolytic-like activity of the latter drug has been attributed to its activity at those receptors. In contrast, yohimbine is an alpha 2 adrenergic antagonist, has negligible affinity for the 5-HT1A receptor, and is generally regarded as being anxiogenic. The present data, which indicate a high degree of similarity between the stimuli induced by yohimbine, 8-OH-DPAT, and ipsapirone, suggest that a re-evaluation of the presumed mechanisms of actions of these drugs is in order.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1985

Generalization of the discriminative stimulus properties of delta 9-THC to delta 9(11)-THC in rats.

Rats were trained in a water maze to discriminate between IP injections of 3 mg/kg delta 9-tetrahydrocannabinol (delta 9-THC) and its vehicle. Both delta 8- and delta 9(11)-THC were generalized to the training drug. In contrast to our observations in rhesus monkeys, where delta 9(11)-THC is at least 100 times less potent than delta 9-THC, delta 9(11)-THC was found to be only seven times less potent in the rat. Relative potencies, expressed as the dosage at which 50% of the animals gave drug responses (ED50) were 1.8 mg/kg and 12.2 mg/kg for delta 9- and delta 9(11)-THC respectively. Twenty-four hours after receiving 7 X ED50 = 12 mg/kg delta 9-THC the tests showed intermediate results when conducted with the training dosage; 4 X ED50 = 50 mg/kg delta 9(11)-THC 48 h prior to the training dosage of 3 mg/kg delta 9-THC completely blocked drug-appropriate responses. Coinjection of ED50 dosages of delta 9- and delta 9(11)-THC led to 90% drug responses, demonstrating the additivity of the cannabis-like effect of both cannabinoids. Differences in the individual sensitivity of the rats to the tested cannabinoids were observed. Findings are interpreted in terms of the receptor mechanism for cannabis-like activity.

Animals↗
PubMed2005

Early and late mechanisms of surround suppression in striate cortex of macaque.

The response of a neuron in striate cortex to an optimally configured visual stimulus is generally reduced when the stimulus is enlarged to encroach on a suppressive region that surrounds its classical receptive field (CRF). To characterize the mechanism that gives rise to this suppression, we measured its spatiotemporal tuning, its susceptibility to contrast adaptation, and its capacity for interocular transfer. Responses to an optimally configured grating confined to the CRF were strongly suppressed by annular surrounding gratings drifting at a wide range of temporal and spatial frequencies (including spatially uniform fields) that extended from well below to well above the range that drives most cortical neurons. Suppression from gratings capable of driving cortical CRFs was profoundly reduced by contrast adaptation and showed substantial interocular transfer. Suppression from stimuli that lay outside the spatiotemporal passband of most cortical CRFs was relatively stronger when the stimulus on the CRF was of low contrast, was generally insusceptible to contrast adaptation, and showed little interocular transfer. Our findings point to the existence of two mechanisms of surround suppression: one that is prominent when high-contrast stimuli drive the CRF, is orientation selective, has relatively sharp spatiotemporal tuning, is binocularly driven, and can be substantially desensitized by adaptation; the other is relatively more prominent when low-contrast stimuli drive the CRF, has very broad spatiotemporal tuning, is monocularly driven, and is insusceptible to adaptation. Its character suggests an origin in the input layers of primary visual cortex, or earlier.

Animals↗