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Acquired equivalence and distinctiveness of cues using a sensory-preconditioning procedure.

In Experiment 1 rats were presented with two flavours, A and B, that were accompanied either by a third common flavour, X, or by two different flavours, X and Y, respectively. An aversion was then established to A, and the extent to which this aversion generalized to B was measured. Stimulus generalization was found to be more marked when A and B had both been presented with the same flavour, X, during pre-exposure than when A and B had been presented with X and Y. In Experiment 2 three target flavours, A, B, and C, were initially presented. In one pre-exposure condition presentations of A and B were accompanied by X, and C was presented alone; in a second condition A and B were presented in isolation, and C was accompanied by X. After an aversion had been established to A, half of the animals in each of the pre-exposure conditions were tested with B, and the remainder were tested with C. In both of the pre-exposure conditions the generalized aversion was more substantial to B than to C. An analysis of these results in terms of the mechanisms that have been supposed to underlie sensory preconditioning is presented.

Animals↗

Further investigation of the discriminative stimulus properties of MDA.

Rats trained to discriminate either (+)-amphetamine or (+/-)-MDA from saline in a two-lever drug discrimination task, were used to study the stimulus effects of MDA and its two optical isomers. Amphetamine-stimulus generalization occurred to S(+)-MDA, but not to its enantiomer R(-)-MDA. This, coupled with our earlier finding of DOM-stimulus generalization to R(-)-MDA but not to S(+)-MDA, suggests that the stimulus effects of S(+)-MDA are predominantly amphetamine-like while those of R(-)-MDA are more DOM-like. Thus, animals trained to discriminate racemic MDA from saline can apparently recognize members of both classes of agents.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

Temporal coding mediates discrimination of "bitter" taste stimuli by an insect.

The mechanisms that mediate discriminative taste processing in insects are poorly understood. We asked whether temporal patterns of discharge from the peripheral taste system of an insect (Manduca sexta caterpillars; Sphingidae) contribute to the discrimination of three "bitter" taste stimuli: salicin, caffeine, and aristolochic acid. The gustatory response to these stimuli is mediated exclusively by three pairs of bitter-sensitive taste cell, which are located in the medial, lateral, and epipharyngeal sensilla. We tested for discrimination by habituating the caterpillars to salicin and then determining whether the habituation generalized to caffeine or aristolochic acid. We ran habituation-generalization tests in caterpillars with their full complement of taste sensilla (i.e., intact) and in caterpillars with ablated lateral sensilla (i.e., lat-ablated). The latter perturbation enabled us to examine discrimination in caterpillars with a modified peripheral taste profile. We found that the intact and lat-ablated caterpillars both generalized the salicin-habituation to caffeine but not aristolochic acid. Next, we determined whether this pattern of stimulus-generalization could be explained by salicin and aristolochic acid generating distinct ensemble, rate, temporal, or spatiotemporal codes. To this end, we recorded excitatory responses from the bitter-sensitive taste cells and then used these responses to formulate predictions about whether the salicin-habituation should generalize to caffeine or aristolochic acid, separately for each coding framework. We found that the pattern of stimulus generalization in both intact and lat-ablated caterpillars could only be predicted by temporal coding. We conclude that temporal codes from the periphery can mediate discriminative taste processing.

Animals↗

TFMPP may produce its stimulus effects via a 5-HT1B mechanism.

Tests of stimulus generalization were conducted using rats trained to discriminate 1.0 mg/kg of 1-(3-trifluoromethylphenyl)piperazine (TFMPP) from saline in a standard two-lever operant procedure. Generalization of the TFMPP-stimulus was found to occur with fenfluramine and 1-(3-chlorophenyl)-piperazine (mCPP); generalization did not occur with 8-OH DPAT, quipazine, LSD, 5-OMe DMT or 2,5-DMA. Furthermore, the TFMPP-stimulus was not antagonized by pretreatment of the animals with tetrahydrotrazodone (THT). Based on the results of these studies, and on the results of previous binding studies with these same agents, it is suggested that the stimulus properties of TFMPP are mediated primarily via a 5-HT1B mechanism.

Animals↗

Stimulus properties of PMMA: effect of optical isomers and conformational restriction.

para-Methoxymethamphetamine (PMMA), a structural hybrid of two central stimulants, lacks stimulant properties but behaves in a manner similar to that of MDMA [N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane]. PMMA has been established as a training drug in drug discrimination studies, and in the present investigation we sought to determine which optical isomer of PMMA is primarily responsible for its stimulus effects. Because PMMA is a conformationally flexible molecule, it was also of interest to determine what conformation is most important for its actions. Accordingly, we prepared and examined S(+)PMMA, R(-)PMMA, and conformationally restricted forms of PMMA: PMMA-AT, TIQ-1, and TIQ-2. S(+)PMMA (ED50 = 0.32 mg/kg) was found to be at least as potent as PMMA (ED50 = 0.41 mg/kg), whereas R(-)PMMA failed to result in complete stimulus generalization. An aminotetralin-like conformation, as found in PMMA-AT (ED50 = 0.29 mg/kg), seems to better account for the actions of PMMA than a tetrahydroisoquinoline-like conformation because TIQ-1 and TIQ-2 failed to result in stimulus generalization. The results of the present study further support the concept that PMMA and MDMA share considerable similarity with respect to their stimulus properties in animals except that PMMA lacks the amphetaminergic stimulant component of action associated with MDMA.

Animals↗

Reduction of visually-induced motion sickness elicited by changes in illumination wavelength.

This experiment was undertaken to assess the degree of stimulus generalization in visually-induced motion sickness. Sixteen subjects participated in six sessions in which they were exposed to a rotating field of vertical stripes for five 4-min trials. This stimulus elicited the perception of self-vection. In the first three sessions, the stripes were illuminated by one monochromatic light (red or green) and in the last three sessions, the stripes were illuminated by the other monochromatic light. Magnitude estimates of motion sickness increased significantly within sessions, but the rate at which this measure increased was significantly diminished across trials in the last three-session block. Magnitude estimates of vection increased within sessions and decreased across sessions, but did not increase with color change. These results can be explained in terms of a model of stimulus generalization and have implications for the reduction of motion sickness in applied settings.

Adolescent↗

Influence of reinforcer type and route of administration on gamma-hydroxybutyrate discrimination in rats.

RATIONALE: Possible effects of reinforcer type on the results of drug discrimination studies have not been examined systematically, but different deprivation operations and differentially effective reinforcers might well influence outcomes. OBJECTIVE: Therefore, this study examined the influence of reinforcer (food or water) as well as route of administration (IP or IG) on gamma-hydroxybutyrate (GHB) discrimination. METHODS: Four separate groups of six rats were trained under a resetting fixed-ratio schedule to discriminate between 300 mg/kg GHB and vehicle under these conditions, then generalization tests were conducted with gamma-butyrolactone (GBL), 1,4-butanediol (1,4-BD), ethanol, and ethanol plus 150 mg/kg GHB. RESULTS: Food maintained significantly higher response rates than water, but there were no significant differences among the four training groups in response accuracy or sessions required to meet the discrimination criterion. Training conditions significantly affected the results of stimulus generalization tests. The IG-Water group was most sensitive to a lower dose of GHB, and only the IP-Water group failed to generalize to orally-administered GHB. Gamma-butyrolactone and 1,4-butanediol fully substituted in all except the IP-Food group. Ethanol did not fully substitute for GHB in any group, and the combination of GHB (150 mg/kg) and ethanol did not have additive effects. CONCLUSIONS: These results demonstrate that methodological variables during drug discrimination training can certainly influence the results of stimulus generalization. Future investigations into the behavioral and/or physiological mechanisms that account for these effects are warranted.

4-Butyrolactone↗

Discriminative stimulus properties of MDA analogs.

Rats trained to discriminate (+/-) 2,5-dimethoxy-4-methylphenylisopropylamine (DOM) (1.0 mg/kg) from saline, using a standard two-lever operant task, were challenged with various doses of 3,4-methylenedioxyphenylisopropylamine (MDA) and several related agents. The (+/-)-DOM stimulus generalized to (+/-)-MDA, suggesting that both agents apparently produce similar stimulus cues. Related agents, known to produce effects in man similar to those produced by (+/-)-MDA, also resulted in generalization when administered to the DOM-trained animals, e.g., R(-)-MDA and a methoxylated derivative of (+/-)-MDA, (+/-)-2-OMe-4,5-MDA. DOM stimulus generalization was not observed for S(+)-MDA, the N-monomethyl and alpha-demethyl derivatives of MDA, nor for a metabolite of MDA (i.e., 3-methoxy-4-hydroxyphenylisopropylamine). The results suggest that R(-)- and (+/-)-MDA, as well as (+/-)-2-OMe-4,5-MDA, but not the other derivatives of MDA, are capable of producing behavioral (stimulus) effects common to those produced by the training dose of (+/-)-DOM.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

Generalization of EMG biofeedback training.

Five young adults received audio biofeedback training to reduce trapezius EMG levels while they engaged in reading in an office, seated at a table. A multiple-baseline-across subjects design was employed in two separate studies. After training, all subjects demonstrated reduced EMG levels while reading in a home or library setting. The first study suggested that subjects reduced EMG levels by minimizing movements and altering their postures; the second study systematically demonstrated changes in such behavior, which was correlated with EMG levels. The data provide evidence that EMG biofeedback resulted in response generalization across several motoric classes, and in stimulus generalization from the training setting to the natural environment. The importance of assessing generalization is discussed.

Acoustic Stimulation↗

Listening experience with iterated rippled noise alters the perception of 'pitch' strength of complex sounds in the chinchilla.

Behavioral responses obtained from chinchillas trained to discriminate a cosine-phase harmonic tone complex from wideband noise indicate that the perception of 'pitch' strength in chinchillas is largely influenced by periodicity information in the stimulus envelope. The perception of 'pitch' strength was examined in chinchillas in a stimulus generalization paradigm after animals had been retrained to discriminate infinitely iterated rippled noise from wideband noise. Retrained chinchillas gave larger behavioral responses to test stimuli having strong fine structure periodicity, but weak envelope periodicity. That is, chinchillas learn to use the information in the fine structure and consequently, their perception of 'pitch' strength is altered. Behavioral responses to rippled noises having similar periodicity strengths, but large spectral differences were also tested. Responses to these rippled noises were similar, suggesting a temporal analysis can be used to account for the behavior. Animals were then retested using the cosine-phase harmonic tone complex as the expected signal stimulus. Generalization gradients returned to those obtained originally in the naïve condition, suggesting that chinchillas do not remain "fine structure listeners," but rather revert back to being "envelope listeners" when the periodicity strength in the envelope of the expected stimulus is high.

Acoustic Stimulation↗

Methcathinone: a new and potent amphetamine-like agent.

The purpose of the present investigation was to examine the effect of N-monomethylation of phenylisopropylamine derivatives on amphetamine-like activity. In tests of stimulus generalization using rats trained to discriminate 1.0 mg/kg of (+)-amphetamine from saline, the N-monomethyl derivatives of 1-(X-phenyl)-2-aminopropane, where X = 2,4-dimethoxy (2,4-DMA), 3,4-dimethoxy (3,4-DMA), 2,4,5-trimethoxy (2,4,5,-TMA), and 2-methoxy-4,5-methylenedioxy (MMDA-2), did not produce amphetamine-appropriate responding at the doses evaluated. However, the N-monomethyl derivative of cathinone (i.e., methcathinone), like cathinone, resulted in stimulus generalization. Further studies with this agent revealed that (a) in the amphetamine-trained animals, methcathinone (ED50 = 0.37 mg/kg) is more potent than racemic cathinone or racemic amphetamine (ED50 = 0.71 mg/kg in both cases), (b) methcathinone is capable of inducing release of radioactivity from [3H]dopamine-prelabeled tissue of rat caudate nucleus in a manner similar to that observed with cathinone, amphetamine, and methamphetamine, and (c) methcathinone is more potent than cathinone as a locomotor stimulant in mice as determined by their effect on spontaneous activity. The results of the present study provide evidence for a structural analogy between the prototypic psychostimulants amphetamine/methamphetamine and cathinone/methcathinone, and lend further support to the concept that amphetamine and cathinone correspond in their pharmacological effects.

Alkaloids↗

Molecular features of odorants systematically influence slow temporal responses across clusters of coordinated antennal lobe units in the moth Manduca sexta.

Behavioral studies of olfactory discrimination and stimulus generalization in many species indicate that the molecular features of monomolecular odorants are important for odor discrimination. Here we evaluate how features, such as carbon chain length and functional group, are represented in the first level of synaptic processing. We recorded antennal lobe ensemble responses in the moth Manduca sexta to repeated 100-ms pulses of monomolecular alcohols and ketones. Most units exhibited a significant change in spike rate in response to most odorants that outlasted the duration of the stimulus. Peristimulus data were then sampled over 780 ms for each pulse of all odorants. Factor analysis was used to assess whether there were groups of units with common response patterns. We found that factors identified and represented activity for clusters of units with common temporal response characteristics. These temporally patterned responses typically spanned 780 ms and were often dependent on carbon chain length and functional group. Furthermore, cross-correlation analysis frequently indicated significant coincident spiking even during spontaneous activity. However, this synchrony occurred mainly between units recorded on the same tetrode. In a final analysis, the Euclidean distance between odor responses was calculated for each pair of odorants using factors as dimensions. The distance between responses for any two odorants was maximized by approximately 240 ms. This time course corresponded to the brief sequence of coordinated bursts across the recorded population. The distance during this period was also a function of systematic differences in molecular features. Results of this Euclidian analysis thus directly correlate to previous behavioral studies of stimulus generalization in M. sexta.

Action Potentials↗

Alcohol consumption following bidirectional shifts in body weight in rats.

Weight restriction has frequently been used to induce consumption of pharmacologically significant amounts of alcohol by rats. When previously weight-restricted rats are fed ad lib., however, their alcohol consumption is substantially reduced. This could occur because weight restriction per se causes increased alcohol consumption, or because the stimulus conditions (in this case, largely interoceptive) that were originally associated with drinking have changed, resulting in a stimulus generalization decrement. The present experiment was designed to discriminate between these two possibilities. Two groups of animals, one at free-feeding weight (FFW) and one at 80% FFW were initially trained to drink alcohol in a limited access paradigm. Each group was then divided into two, such that one half remained at its original weight and the other was gradually shifted to the reverse feeding condition in a double cross-over design. When alcohol consumption was again stable the experimental groups were returned to their original weights. If the weight restriction hypothesis were true, animals should drink more when weight-reduced and less when at FFW. According to the stimulus generalization decrement hypothesis, drinking should decrease with any shift from their initial weight. The direction of the results was such as to support the weight restriction hypothesis, but the magnitude of the changes was greater than would be expected on the basis of the respective control groups, and the effects were often transient. In these ways the results more closely resembled positive and negative contrast effects that have traditionally been described following shifts in amount of reinforcement. Possible mechanisms and the importance of an animal's history as a determinant of alcohol consumption are discussed.

Alcohol Drinking↗

Pentazocine, cyclazocine, and nalorphine as discriminative stimuli.

Pentazocine, cyclazocine, and nalorphine are narcotic antagonists that also have analgesic activity of their own. The present investigation compared the stimulus properties of these three drugs in rats. Each drug was used as a discriminative stimulus for a separate group of rats. Depression of one lever resulted in food reinforcement following the administration of drug, and the opposite lever was reinforced after saline. Each drug readily acquired control of discriminated responding. The specific narcotic antagonist, naloxone, which antagonizes many of the effects of pentazocine, cyclazocine, and nalorphine, also antagonized the discrimination of these drugs. Stimulus generalization tests to each other narcotic antagonist, d-amphetamine, morphine, and LSD, showed that each narcotic antagonist has highly specific stimulus properties. Clear generalization occurred only to pentazocine and cyclazocine in the nalorphine-saline group, but neither cyclazocine nor pentazocine generalized to nalorphine.

Animals↗

Discriminative stimulus effects of pentobarbital in rats.

The discriminative stimulus effects of a low dose of sodium pentobarbital (4 mg/kg, sc) were investigated in 10 rats trained to discriminate between the drug and saline under a 2-lever choice procedure. A food pellet was delivered after every 10 depressions of the appropriate lever, which lever was appropriate being determined by whether the drug or saline was administered prior to the daily session. Discrimination of the substances was said to have been attained when more than 8 out of the 1st 10 responses were to the appropriate lever for 10 consecutive days, and 7 rats met the criterion after 43 to 96 sessions. Stimulus generalization tests revealed the stimulus properties of the drug at 4 mg/kg to be similar to those of diazepam 0.25 mg/kg, sc and ethanol 1 g/kg, ig, but not of various doses of d-amphetamine, morphine, pentazocine, chlorpromazine, and imipramine. It was thus found that the rats could discriminate a relatively low dose of pentobarbital and that its stimulus effects do not differ from those at higher doses reported by other investigators.

Animals↗

The effect of the blackout method on acquisition and generalization.

In discrimination training with the Lyons' blackout method, pecks to the negative stimulus are prevented by darkening the chamber each time the subject approaches the negative stimulus. Stimulus generalization along a stimulus dimension was measured after training with this method. For comparison, generalization was also measured after reinforced responding to the positive stimulus without discrimination training, and after discrimination training by extinction of pecks to the negative stimulus. The blackout procedure and the extinction of pecks to the negative stimulus both produced a peak shift in the generalization gradients. The results suggest that after discrimination training in which the positive and negative stimulus are on the same continuum, the blackout method produces extinction-like effects on generalization tests.

Journal Article↗