Conditioning of a discriminative drug stimulus: Overshadowing and blocking like procedures

Interactions between a drug discriminative stimulus ( D , 17.5 mg/kg of pentobarbital vs. N , saline) and exteroceptive stimulus conditions (light vs. dark) were examined in a T-maze, shock-escape task using conditioning procedures pertaining to the phenomena of "overshadowing" and "blocking". From an operational point of view, in the "overshadowing" procedure the stimulus compound is introduced from the outset of the training, whereas in the "blocking" procedure the stimuli components are introduced sequentially. When the compound discriminations were established, dose-generalization tests with various doses of pentobarbital (range 5.6–17.5 mg/kg) as well as saline (1 ml/kg) were carried out under both elements (light and dark) of the exteroceptive stimulus dimension. Prior training with drug ( D vs. N ) neutralized the potential influence of the exteroceptive dimension (light vs. dark); conversely training with the exteroceptive stimuli prior to the drug training accentuated the control over behavior by the visual stimuli. Dose-generalization results intermediate to those described above were observed in the group trained to discriminate the stimulus compound ( D plus light vs. N plus dark) from the outset of training. It may therefore be concluded that exteroceptive stimuli can compete with interoceptive drug stimuli for associative strength in the procedure used. Thus, the formal similarities between drug discriminative stimuli and more conventionally studied exteroceptive, sensory signals are furthered by the data.     

Emergent equivalence relations between interoceptive (drug) and exteroceptive (visual) stimuli.

Conditional "if-then" relations between drug (interoceptive) stimuli and visual (exteroceptive) stimuli were taught to 4 normal humans. Interoceptive stimuli were the effects produced by 0.32 mg/70 kg triazolam (a prototypical benzodiazepine) and placebo (lactose-filled capsules); exteroceptive stimuli were black symbols on white flash cards. Following the training of the prerequisite conditional relations, tests of emergent relations were conducted between exteroceptive stimuli and between interoceptive and exteroceptive stimuli. Equivalence relations emerged immediately without explicit training for all 4 subjects. Accuracy of responding during the interoceptive-exteroceptive equivalence tests and subjects' self-reports showed consistent discrimination between the drug effects of triazolam and placebo. Finally, a generalization test assessed whether a novel visual stimulus presented in the context of the placebo (i.e., no drug) would generalize to visual stimuli belonging to the placebo stimulus class. All 3 subjects who completed this test reliably chose the visual stimuli belonging to the placebo class and not the visual stimuli belonging to the triazolam stimulus class. The development of equivalence relations between interoceptive and exteroceptive stimuli demonstrates that private and public stimulus events can emerge as members of the same equivalence class. Theoretical and clinical implications are discussed.     

A flavor paired with lithium chloride blocks the formation of a pentobarbital-lithium chloride association

Thirsty rats were used in order to determine whether a vinegar solution, which had been paired with an injection of lithium chloride, could block the formation of an association between a pentobarbital- and a lithium chloride-induced state. During phase 1 the rats in the blocking group had a 2.0% vinegar solution paired with an injection of 240 mg/kg of lithium chloride, during phase 2 these rats were reexposed to the vinegar prior to each injection of 20 mg/kg of pentobarbital and 240 mg/kg of lithium chloride, and during phase 3 these rats were given access to a novel 0.75% saccharin solution and were injected with pentobarbital after saccharin removal. Animals with this history did not form an association between the pentobarbital- and lithium chloride-induced states during phase 2 as evidenced by their refusal to consume the saccharin solution over repeated pairings of saccharin with pentobarbital during phase 3. Control groups that received forward pairings of pentobarbital and lithium chloride, in the absence of a previously conditioned vinegar solution during phase 2, formed an association between pentobarbital and lithium chloride. These findings indicate that drug states and flavors can interfere with each others' capacity to predict the occurrence of lithium chloride.     

Consolidation and long-term retention of an implanted behavioral memory

Hypothesized circuitry enabling information storage can be tested by attempting to implant memory directly in the brain in the absence of normal experience. Previously, we found that tone paired with activation of the cholinergic nucleus basalis (NB) does induce behavioral memory that shares cardinal features with natural memory; it is associative, highly specific, rapidly formed, consolidates and shows intermediate retention. Here we determine if implanted memory also exhibits long-term consolidation and retention. Adult male rats were first tested for behavioral responses (disruption of ongoing respiration) to tones (1-15 kHz), yielding pre-training behavioral frequency generalization gradients. They next received 3 days of training with a conditioned stimulus (CS) tone (8.0 kHz, 70 dB, 2s) either paired (n=7) or unpaired (n=6) with moderate electrical stimulation of the nucleus basalis (～ 65 μA, 100 Hz, 0.2s, co-terminating with CS offset). Testing for long-term retention was performed by obtaining post-training behavioral frequency generalization gradients 24h and 2 weeks after training. At 24h post-training, the Paired group exhibited specific associative behavioral memory, manifested by larger responses to the CS frequency band than the Unpaired group. This memory was retained 2 weeks post-training. Moreover, 2 weeks later, the specificity and magnitude of memory had become greater, indicating that the implanted memory had undergone consolidation. Overall, the results demonstrate the validity of NB-implanted memory for understanding natural memory and that activation of the cholinergic nucleus basalis is sufficient to form natural associative memory.     

Effects of stimulus similarity in discrimination training upon wavelength generalization in pigeons.

Thirty pigeons were given variable interval training to peck a 555-nm. light and then were tested for wavelength generalization. The subjects were later assigned to 1 of 3 groups, matched for both relative generalization slope and response rate. One group then received successive discrimination training between the 555-nm. stimulus (S+) and a vertical white line on a 555-nm. background (S minus); another group experienced the same S+ but a vertical white line on a black background as S minus. A third group received a comparable amount of single stimulus training with the 555-nm. value. On a second wavelength generalization test, the first group yielded greater sharpening of generalization than the second group, whereas the third group showed no change from Test 1. These results indicate that the sharpening of generalization gradients by discrimination training is directly related to the similarity of the discrimination training stimuli.     

Stimulus generalization of conditioned taste aversion in rats

Relatively little information is available regarding the intradimensional stimulus generalization of conditioned taste aversion (CTA). Experiment 1 employed a between-groups generalization test to examine the extent to which conditioned flavor aversion to one sucrose solution generalized to other concentrations of sucrose in adult rats. Evidence of a gradient of aversion was obtained. Because generalization gradients in other tasks have been found to flatten over a retention interval, Experiment 2 investigated the effects of delayed testing (2, 7, or 21 days) upon the slope of the generalization gradient. The generalization gradient flattened at the intervals, suggesting that subjects forgot the specific attributes of the conditioning concentration and avoided generalized stimuli as if they were the original CS. Experiment 3 used a long delay between taste and toxicosis to degrade the associative contingency and found no evidence that the generalization gradients found in the first two experiments could be explained in terms of enhanced neophobia due to poisoning. These findings provide further evidence (cf. A. W. Logue, 1979, Psychological Bulletin, 86, 276-296; M. Domjan, 1980, in J. S. Rosenblatt, R. A. Hinde, C. Beer, & M. Busnel (Eds.), Advances in the study of behavior, Vol. 11, New York: Academic Press) that CTA shares a number of similarities with other learning processes. Further, they illustrate that stimulus forgetting can be detected in a paradigm considered relatively immune to retention loss.     

Effects of reserpine on retention of escape reversal in mice: absence of state-dependent learning.

A discriminated escape training paradigm was used to study the effects of reserpine on learning and memory in mice. Intraperitoneal injection of reserpine before reversal training had no effect on acquisition but did produced a time-and dose-dependent impairment of retention test performance 10 days later. These results suggested that reserpine may have interfered with some aspect of memory storage. Retention impairments observed when a 2.0 mg/kg reserpine injection was given 2 hr before reversal training were not attenuated by readministering the drug before testing, a finding that provides no support for a state-dependency interpretation. Furthermore, animals treated with reserpine exhibited inferior retention of previous training, regardless of the pharmacological state present during that learning. This was interpreted as a drug-induced impairment of memory retrieval. In addition, performance during the initial discriminated escape training session suggested that reserpine may also impair acquisition under some conditions. In the last experiment, it was found that when the catecholamine precursor L-dihydroxyphenylalamine (100 mg/kg) and the indole amine precursor D,L-5-hydroxytryptophan (125 mg/kg) were both given after reserpine treatment, subsequent retention performance was not significantly impaired. The results are discussed in terms of the possible roles of biogenic amines in arousal, learning, and memory.     

Learning of rats under amnesia caused by pentobarbital.

Dissociated learning of rats in the normal state and the state of amnesia produced by pentobarbital (15 mg/kg, ip) was carried out. Rats were trained to approach a shelf where they received food reinforcement. In Group 1 the rats were trained under the influence of pentobarbital to run to the same shelf as in the normal state. In Group 2 the rats were trained to approach different shelves in different drug states. It was shown that memory dissociation occurred in both groups. Differences in the parameters of training under the influence of pentobarbital between Groups 1 and 2 were revealed. These findings show that the brain-dissociated state induced by pentobarbital is formed with the participation of the mechanisms of information perception.     

Opposite effects of a single versus repeated doses of gabapentin on retention performance of an inhibitory avoidance response in mice

CF-1 male mice were trained in an inhibitory avoidance (IA) task. A single gabapentin (GBP) administration (50mg/kg, ip) immediately after training enhanced retention performance when mice were tested 8 days after training. On the contrary, when the same dose of the anticonvulsant drug was given twice a day for 7 days (repeated treatment), a significant impairment on retention performance 12h after the last injection of GBP was observed. When the retention test was delayed 7 days after the end of the repeated treatment, the retention performance was not significant different from the control group, whereas if the retention test was delayed 14 days, retention performance was higher than control group but similar to that observed when GBP was administered once immediately after training. The impairment on retention performance was correlated with a significant decrease in the high affinity choline uptake in the hippocampus at the end of the retention test. The pretest administration of the direct muscarinic cholinergic agonist oxotremorine (50 microg/kg, ip) reversed the impairment on retention performance. This reversion was prevented by the muscarinic cholinergic antagonist scopolamine (0.5 mg/kg, ip). Taken together, these results suggest that the impairment on retention performance of an IA task in mice induced by repeated administration of GBP affected memory retrieval but not memory consolidation and that this impairment may be attributable to a reduction on central cholinergic activity.     

Effects of neophobia and habituation on the poison-induced avoidance of exteroceptive stimuli in the rat.

Two experiments on the role of neophobia in poison-induced aversions to exteroceptive stimuli are reported. In Experiment 1, rats were given either 10 or 25 days of habituation to the test situation prior to conditioning. Those animals with the longer habituation period avoided a complex of novel exteroceptive stimuli while those with the shorter habituation period did not. In Experiment 2 rats initially avoided the more novel of two containers, but gradually came to eat equal amounts from both. A single pairing of toxicosis with consumption from either the novel or the familiar container reinstated the avoidance of the novel container in both cases. The results were discussed in terms of an interaction between habituation and conditioning procedures. It was suggested that previously reported differences between interoceptive and exteroceptive conditioning effects may have been influenced by the differential novelty of the two classes of stimuli in the test situation. It was further suggested that non-contingently poisoned control groups should routinely be included in poison avoidance conditioning studies.     

Effects of body weight on discriminative-stimulus control by phencyclidine in the pigeon.

Using a color-tracking procedure with responses reinforced under a second-order schedule, the discriminative-stimulus properties of phencyclidine were studied in pigeons maintained at 70%, 80%, or 90% of their free-feeding weights. The generalization curves for phencyclidine were similar at all three body weights. Generalization curves for pentobarbital, d-amphetamine, and saline were also unrelated to body weight. These data suggest that food deprivation may not influence the discriminative-stimulus properties of drugs in the way that it influences the reinforcing-stimulus properties of drugs. The reason may be that during discrimination training interoceptive stimuli resulting from food deprivation do not become conditioned to the stimulus properties of the drug, because the food-deprivation stimuli are paired equally often with the presence and absence of drug stimuli.     

The ontogeny of auditory frequency generalization in the chicken.

To determine if there is an ontogenetic change in stimulus coding, chickens between the day of hatching and 9-10 days old were tested using a habituation-generalization paradigm. Experiment 1 indicated that 1 day-old and 3--4-day-old chicks show similar habituation of an eye-opening response to auditory stimuli in the 800--1,200-Hz range. In Experiment 2 the eye-opening response to a 1,000-Hz stimulus was habituated and then immediately tested using stimuli which varied between 800 and 1,200 Hz. Each age-group (1 day, 3--4 days, and 9--10 days) showed a symmetrical stimulus generalization gradient around the 1,000-Hz stimulus and the 1-day-old chicks displayed a reliably flatter gradient than either of the older groups, which did not differ. In a third experiment, the position of the gradients relative to the baseline was shifted without altering the relative shapes. These results allow general arousal, general auditory responsiveness, overall error rate, and metric characteristics of the independent and dependent variables to be eliminated as possible sources of the age differences in gradient shape. The changes in stimulus generalization, therefore, support the view that during normal development there is a sharpening of perceptual coding processes.     

Stimulus control of differential-reinforcement-of-low-rate responding

Five pigeons were given single-stimulus training on an 8-sec differential-reinforcement-of-low-rate schedule followed by steady-state generalization training using 12 wavelength stimuli. Three birds had a high percentage of reinforced responses on the training schedule and flat generalization gradients of total responses. The birds with fewer reinforced responses had much steeper generalization gradients. Generalization gradients plotted as a function of both stimulus wavelength and interresponse time showed that for most birds, stimulus control was restricted to responses with long interresponse times. Responses with very short interresponse times were not under stimulus control and there was some evidence of inhibitory control of short interresponse times. Interresponse-times-per-opportunity functions, plotted as a function of stimulus wavelength, showed that stimulus wavelength controlled the temporal distribution of responses, rather than the overall rate of response. The data indicate that the differential-reinforcement-of-low-rate schedule generates several response categories that are controlled in different ways by wavelength and time-correlated stimuli, and that averaging responses regardless of interresponse-time length obscures this control.     

Long-term memory in pigeons: I. The role of discrimination problem difficulty assessed by reacquisition measures II. The role of stimulus modality assessed by generalization slope

Pigeons learned either an easy or a difficult line angle discrimination (Experiment 1) or wavelength discrimination (Experiment 2), and then they were given a reacquisition test of retention after delays of 1 min, 1 day, or 1 week. Both percentage of responses to the S+ in the initial 10-trial block and number of blocks to criterion showed a progressive memory loss which was greater for the difficult problem. These results extend recent findings by using a free operant rather than a discrete trial task and by varying problem difficulty by altering the dimensional separation between training stimuli. In Experiment 3, pigeons were given variable interval training with either a wavelength or a line angle stimulus, and then they were tested for generalization in extinction after delays of 1 min, 1 day, and 1 week. With both dimensions, the relative gradients became progressively flatter with increasing delay intervals. This replicates earlier findings and extends them to the line angle dimension. The evidence of substantial forgetting in the first 24 h in all three experiments suggests that operant free-response procedures are more sensitive to forgetting effects than are discrete trial tasks.     

Response suppression by visual stimuli paired with postsession d-amphetamine injections in the pigeon

Responding of pigeons, maintained under a fixed-interval 3-minute schedule of food presentation, was decreased on days that the color of the lights illuminating the food magazine was changed and d-amphetamine (1.0 mg/kg, i.m.) was injected after the session. Responding was not decreased by keylight color changes paired with postsession d-amphetamine or by postsession injections of saline. Administration of pentobarbital (3.0 to 5.6 mg/kg), but not d-amphetamine (.3 to 3.0 mg/kg), before the session increased rates of responding suppressed by drug-paired magazine lights. Responding maintained under a fixed-ratio 30-response schedule was not decreased when differently colored magazine lights were paired with a low (.3 mg/kg) postsession dose of d-amphetamine; with high (3.0 mg/kg) postsession doses, however, responding was completely suppressed after two pairings. The effects of pairing magazine stimuli with an intermediate (1.0 mg/kg) postsession dose of d-amphetamine depended upon the magnitude of prior postsession doses. After being paired with a low dose, stimuli paired with 1.0 mg/kg did not suppress responding. After being paired with a high dose, stimuli paired with 1.0 mg/kg completely suppressed responding. The suppression of food-maintained responding by stimuli paired with postsession drug administration depends upon both behavioral and pharmacological variables.     

Stimulus generalization following extra-dimensional training in educationally subnormal (severely) children.

The use of discrimination learning paradigms in the study of attentional transfer is discussed. The technique of go/no-go discrimination learning followed by stimulus generalization testing is contrasted with the more familiar simultaneous learning paradigm followed by a shift in the relevant cues. In the former paradigm the effect of training a discrimination on one dimension on the slope of the stimulus generalization gradient on an independent gradient dimension (extra-dimensional training) is assessed. A steepening of the gradient relative to appropriate control procedures is taken as evidence of positive attentional transfer. The relevance of the technique to the detailed study of attentional transfer in educationally subnormal (severely) (ESN(S)) children is considered. In Expt. I nine ESN(S) children were trained in a go/no-go discrimination involving stimuli differing in orientation, and were generalization tested on a dimension that was orthogonal, namely hue. Of the six subjects who learnt the discrimination five showed clear decremental gradients on the hue dimension. In contrast a Pseudo-Discrimination group (PD) of eight subjects matched to those in the TD group showed no gradients. These subjects were not trained in the orientation discrimination, but were reinforced for responding on 50 per cent of each of the S+ and S- stimulus presentations. They thus received equal exposure to, but no differential training on, the orientation dimension. An S+ only group of four subjects who received no exposure to the orientation stimuli showed no gradients when stimulus generalization testing on the hue continuum was carried out. The result is discussed in terms of transfer deriving from stimulus control by relational aspects of the stimuli; in terms of control by constant irrelevant stimuli; and in terms of the study of stimulus control in ESN(S) children. In Expt. II the influence of the codability of the colours on the location of the peak of the stimulus generalization gradients in the TD group is investigated.     

Drug states as discriminative stimuli in a flavor-aversion learning experiment

Injection of poison into rats after they drank in the presence of stimulus compounds of a drug state and a flavor resulted in little stimulus control by the drug state. In Experiment 1, half of the rats were poisoned after drinking salt water while stimulated with amphetamine and after drinking sugar water while sedated with pentobarbital, but they were not poisoned after salt-pentobarbital or sugar-amphetamine combinations. The other half were subjected to counterbalanced procedures. In abstract language, poisoning occurred after AX and BY stimulus combinations but did not occur after AY and BX combinations. In Experiment 2A, rats were poisoned only after consuming a particular flavored solution (salt or vinegar) in a particular state (pentobarbital or undrugged); that is, if AX was poisoned, BX, BY, and AY were experienced without poisoning. There was complete counterbalancing of flavors and drug states. Experiment 2B was similar except that amphetamine was used instead of pentobarbital. In both experiments, there was some discrimination learning based on the drug state, gut it was extremely weak.     

Some effects on generalization gradients of tandem schedules

The relationship between training conditions and stimulus generalization gradients was examined using tandem schedules of reinforcement. Schedules were selected so that frequency of reinforcement and rate of responding were varied somewhat independently of each other. A peak-shift in the generalization gradient was obtained when extinction had been associated with one of the stimuli. No comparable peak shift was obtained when there were equal response rates in the training stimuli even with dissimilar frequencies of reinforcement. The data imply that response rates at the end of training, rather than reinforcement frequency per se, determine the characteristics of the generalization gradient.     

Auditory frequency generalization in the goldfish (Carassius auratus)

Auditory frequency generalization in the goldfish was studied at five points within the best hearing range through the use of classical respiratory conditioning. Each experimental group received single-stimulus conditioning sessions at one of five stimulus frequencies (100, 200, 400, 800, and 1600 Hz), and were subsequently tested for generalization at eight neighboring frequencies. All stimuli were presented 30 db above absolute threshold. Significant generalization decrements were found for all subjects. For the subjects conditioned in the range between 100 and 800 Hz, a nearly complete failure to generalize was found at one octave above and below the training frequency. The subjects conditioned at 1600 Hz produced relatively more flat gradients between 900 and 2000 Hz. The widths of the generalization gradients, expressed in Hz, increased as a power function of frequency with a slope greater than one.     

Retention deficit after d-amphetamine treatment: memory defect or performance change?

Retention deficits in discrete trial delayed alternation and delayed matching to sample tasks following administration of d-amphetamine have been interpreted to support the view that arousal facilitates the decay of information from shortterm memory (STM) (Kesner, 1973). But since amphetamine causes numerous changes in performance, alternative explanations of the deficit are also plausible. In an attempt to separate drug effects on memory from those on performance, the effects of d-amphetamine on spatial memory in the radial maze were studied in rats. The unusually long span of accurate working memory in this setting permits drug administration within the retention interval as well as prior to the to-be-remembered event (TBRE). In rats tested at a 5-hr retention interval d-amphetamine (2 mg/kg) disrupted retention when given 0.5 hr before or 4.5 hr after the TBRE, but the same treatment 0 or 2 hr after the TBRE or 3 hr before the TBRE was without effect. At a 5-hr retention interval 3 mg/kg d-amphetamine impaired performance if given 2 hr after the TBRE, but not when given 0 hr after the TBRE or 3 hr before the TBRE. However, when the retention interval was lengthened to 7 hr, administering 3 mg/kg d-amphetamine 2 hr after the TBRE did not disrupt performance. The effects of d-amphetamine on spatial memory are best explained in terms of the well established effects of the drug on motor activity and appetite. Similar changes in performance may account for the "memory" impairments observed after amphetamine treatment in other tasks.