Variability in prescription opioid intake and reinforcement amongst 129 substrains.

Opioid abuse in the United States has reached epidemic proportions, with treatment admissions and deaths associated with prescription opioid abuse quadrupling over the past 10 years. Although genetics are theorized to contribute substantially to inter-individual variability in the development, severity and treatment outcomes of opioid abuse/addiction, little direct preclinical study has focused on the behavioral genetics of prescription opioid reinforcement and drug-taking. Herein, we employed different 129 substrains of mice currently available from The Jackson Laboratory (129S1/SvlmJ, 129X1/SvJ, 129S4/SvJaeJ and 129P3/J) as a model system of genetic variation and assayed mice for oral opioid intake and reinforcement, as well as behavioral and somatic signs of dependence. All substrains exhibited a dose-dependent increase in oral oxycodone and heroin preference and intake under limited-access procedures and all, but 129S1/SvlmJ mice, exhibited oxycodone reinforcement. Relative to the other substrains, 129P3/J mice exhibited higher heroin and oxycodone intake. While 129X1/SvJ exhibited the highest anxiety-like behavior during natural opioid withdrawal, somatic and behavior signs of precipitated withdrawal were most robust in 129P3/J mice. These results demonstrate the feasibility and relative sensitivity of our oral opioid self-administration procedures for detecting substrain differences in drug reinforcement/intake among 129 mice, of relevance to the identification of genetic variants contributing to high vs. low oxycodone reinforcement and intake.

Detection errors on the word the: evidence for reading units larger than letters.

In four experiments, subjects read 100-word passages and circled instances of the letter t. Subjects missed a disproportionate number of ts in the word the. Evidence was provided against explanations of this effect involving the location and pronunciation of the t in the and against an explanation in terms of the redundancy of the. Rather the high frequency of the appeared to be critical, and it was suggested that high-frequency words are read in terms of units larger than the letter.

A secondary-task analysis of a word familiarity effect.

In three experiments we examined aspects of the word inferiority effect and word frequency disadvantage for letter detection. In Experiment 1 we tested a prediction derived from a hypothesis based solely on attentional factors. Adult subjects performed one of two secondary detection tasks while reading for comprehension. The inferiority effects were obtained only when the secondary task was letter detection, not when nonletter targets were used in the secondary task. This finding is inconsistent with the attentional hypothesis, but is consistent with the unitization hypothesis of Healy and Drewnowski (1983). In Experiments 2 and 3 we found that manipulation of the need to read for comprehension had little influence on the letter-detection inferiority effects, but a strong influence on the effects involving the detection of nonletter targets. These results are discussed in terms of their implications concerning processing system flexibility.

Context independence and phonetic mediation in categorical perception.

Categorical perception, as an ideal situation, is rarely if ever observed in the laboratory. Two separate requirements must be met for categorical perception: (a) Discrimination performance must be phonetically mediated (i.e., it should be predictable from labeling performance), (b) labeling responses must be independent of the stimulus context. To determine the extent to which departures from the ideal are due to failures to meet one or both of these requirements, we used four stimulus continua in same-different (AX) discrimination and labeling tasks: stop-consonant-vowel (CV) syllables, isolated vowels, isolated fricative noises, and nonspeech sounds varying in timbre. We found that perception of CV syllables fell short of the ideal only because of contextual influences on labeling. Neither criterion of categorical perception was met by vowels or fricative noises, but subjects were more prone to phonetic mediation with vowels than with fricative noises, and they showed more context independence with fricative noises than with vowels. Surprisingly, the nonspeech timbre stimuli satisfied both requirements better than either vowels or fricative noises. This findings was attributed to the short duration of our timbre stimuli, which prevented them from sounding vowel-like but at the same time may have prevented stable auditory memory traces.

Investigating the boundaries of reading units: letter detection in misspelled words.

In two experiments, subjects searching for the letter t in passages that contained some misspellings made many more errors on the word the than on other correctly spelled words. Accuracy increased dramatically when the word the and the other words containing t were misspelled, even when the misspelled word was the same shape as the original. These findings define a word-inferiority effect, which stands in contrast to the superior perception of letters in words over nonwords commonly found in tachistoscopic studies. In a third experiment, subjects searched for the letter n in passages typed normally or typed with all interword spaces replaced by the symbol +. Detection errors on the word and were greatly reduced when the interword spaces were replaced by +s, but errors on other words, including those ending in the suffix morpheme -ing, were not affected by this manipulation. These results suggest that frequent function words are processed in terms of reading units that are larger than the letter and include the interword spaces.

Categories and context in the perception of isolated steady-state vowels.

The noncategorical perception of isolated vowels has been attributed to the availability of auditory memory in discrimination. In our first experiment, using vowels from an /i/-/I/epsilon) continuum in a same-different (AX) task and comparing the results with predictions derived from a separate identification test, we demonstrated that vowels are perceived more nearly categorically if auditory memory is degraded by extending the interstimulus interval and/or filling it with irrelevant vowel sounds. In a second experiment, we used a similar paradigm, but in addition to presenting a separate identification test, we elicited labeling responses to the AX pairs used in the discrimination task. We found that AX labeling responses predicted discrimination performance quite well, regardless of whether auditory memory was available, whereas the predictions from the separate identification test were more poorly matched by the obtained data. The AX labeling reponses showed large contrast effects (both proactive and retroactive) that were greatly reduced when auditory memory was interfered with. We conclude from the presence of these contrast effects that vowels are not perceived categorically (that is, absolutely). However, it seems that by taking the effects of context into account properly, discrimination performance can be quite accurately predicted from labeling data, suggesting that vowel discrimination, like consonant discrimination, may be mediated by phonetic labels.

Detecting letters in continuous text: effects of display size.

In three letter detection experiments, subjects responded to each instance of the letter t in continuous text typed in a standard paragraph, typed with one to four words per line, or shown for a fixed duration on a computer screen either one or four words at a time. In the multiword and the standard paragraph conditions, errors were greatest and latencies longest on the word the when it was correctly spelled. This effect was diminished or reversed in the one-word conditions. These findings support a set of unitization hypotheses about the reading process, according to which subjects do not process the constituent letters of a word once that word has been identified unless no other word is in view.

Order-relevant and order-irrelevant decision rules in multiletter matching.

Two experiments examined order effects in multiletter matching. In each experiment, subjects used one of two decision rules that differed in whether pairs of letter strings that contained the same letters, but in different orders (rearranged pairs), were classified as same or different. Method of presentation also was varied, with the two strings in each pair being presented either simultaneously or successively in one experiment, and with the exposure duration of the second of two successively presented strings being either short or long in the other. Latency and accuracy of responding to the rearranged pairs varied as a function of the amount of positional displacement, with the two tasks showing similar, but mirror image, patterns. This outcome suggests that most of the order effects are attributable to processes common to both tasks, although there was some evidence for a contribution from task-specific processes as well. Both method-of-presentation manipulations had little influence on the order effects, suggesting that the effects are attributable to perceptual and decision processes, rather than to memory processes. The results are most consistent with a model that assumes position-sensitive comparisons, with the same-different decision based on pooled information.

Semantic, phonological, and mediated priming in reading and lexical decisions.

Four experiments were conducted to investigate whether semantic activation of a concept spreads to phonologically and graphemically related concepts. In lexical decision or self-paced reading tasks, subjects responded to pairs of words that were semantically related (e.g., light-lamp), that rhymed (e.g., lamp-damp), or that combined both of these relations through a mediating word (e.g., light-damp). In one version of each task, test lists contained word-word pairs (e.g., light-lamp) as well as nonword-word (e.g., pown-table) and word-nonword pairs (e.g., month-poad); in another version, test lists contained only word-word pairs. The lexical decision and self-paced reading tasks were facilitated by semantic and rhyming relations regardless of the presence or absence of nonwords on the test lists. The effect of the mediated relation, however, depended on the presence of nonwords among the stimuli. When only words were included, there was no effect of the mediated relation, but when nonwords were included, lexical decision and self-paced reading responses were inhibited by the mediated relation. These inhibitory effects are attributed to processes occurring after lexical access, and the relative advantages of the self-paced reading task are discussed.

Processes underlying long-term repetition priming in digit data entry.

Two experiments examined long-term repetition priming in data entry. In each experiment, participants entered 4-digit numbers displayed as either words or numerals, and responded with digits (Experiment 1), or either digits or initial letters (Experiment 2). At test 1 week later, they entered old and new numbers, with the format changed for half of the old stimuli. Implicit memory was evidenced at test by faster entry of the old than the new numbers, regardless of whether the numbers were in the same or different format, suggesting that the abstract numerical meaning, not the surface form, contributes to repetition priming. Numbers presented as words in training had an advantage over numbers presented as numerals, regardless of response format, implying that type of processing also contributes to the effect and ruling out an explanation based on time spent processing numbers in word format.

Learning of nondomain facts in high- and low-knowledge domains.

Research on expertise has repeatedly documented that experts learn new information better than do novices, but only when the information is relevant to the expert's domain. It was found in Experiment 1 that participants showed superior learning and recall of a large quantity of new, non-domain-relevant facts about concepts within their domain of high knowledge than about concepts for which they had low domain knowledge. Experiment 2 investigated whether the participants' superior recall of new facts related to concepts within their domain of high knowledge was due to the number of prior facts associated with the concept or to the prior frequency of repetition of those concepts. It was found that participants' recall of new facts was better for concepts with 5 prior associated facts than for concepts with a single prior association but that the number of previous repetitions of each concept did not affect the level of recall for the new facts.

Effects of repetition on short-term retention of order information.

Two experiments examined the effects of repetition on the short-term retention of order information. A partial report procedure was coupled with the distractor paradigm to vary which one of two 4-letter sequences was tested after a digit-filled retention interval. Repeatedly presenting the stimulus but not its testing did not increase recall, but recall did increase when both presentation and testing were repeated. Recall was also improved by precues that informed subjects in advance which sequence was to be recalled. The perturbation model of Estes (1972; Lee & Estes, 1981) was able to account for the qualitative and quantitative aspects of the results by making an explicit distinction between two types of rehearsal: the reactivation process, which corresponds to a passive, automatic rehearsal process; and an active, conscious rehearsal process that crystallizes the memory structure and makes perturbations less likely.

Long-term repetition effects for motoric and perceptual procedures.

Two experiments examined the relationship between implicit and explicit measures of memory for information encoded in a motoric task, called data entry. In both experiments, subjects entered lists of digit sequences with a computer keypad. They were retested on the same task after a delay of up to 1 month. At retention, implicit memory for the digit lists was evidenced by faster entry of old relative to new lists in both experiments. In Experiment 1, subjects were able to discriminate old from new lists. Recognition memory of old lists was better after than before entering the lists. In Experiment 2, perceptual and motoric contributions to the old/new difference in typing speed were isolated by means of a transfer paradigm. The results showed that the entry-speed advantage for the old lists was due to the separate reinstatement at the retention test of both perceptual and motoric procedures encoded earlier. Implicit and explicit measures of memory were found to be dependent rather than independent. The findings from this study are interpreted within a framework of memory based on procedural reinstatement.

Acquisition and retention of a letter-detection skill.

In two experiments, we examined the acquisition and retention of a letter-detection skill with a consistent-mapping procedure. In Experiment 1, subjects were trained from 0 to 4 sessions at detecting the letter H in displays containing random letters, and retesting occurred after a 1-month delay. Performance improved and in some cases became more automatic, and the performance level was maintained over the retention interval. When tested with a prose passage, the high error rate on the word THE was eliminated after training and after the retention interval, regardless of the amount of training. In Experiment 2, two subjects were given 12 sessions of training followed by a retention test 6 months later. For 1 subject there was also a retention test 15 months after acquisition. Performance improved dramatically with training, and substantial but not complete automaticity was achieved. Performance on the retention tests was close to the final acquisition level. The surprising lack of forgetting in this study was contrasted with the substantial forgetting typically found in studies of verbal learning.

Facilitating text memory with additional processing opportunities in rapid sequential reading.

Previous research indicates that during conventional reading, readers pause at particular loci within a text, presumably for the purpose of higher level processing and integration. If such pausing is necessary for efficient text comprehension and memory, then providing readers with equivalent processing opportunities with strategically placed pauses in rapid sequential visual presentation (RSVP) text displays should facilitate comprehension and memory. Three experiments are reported in which various time parameters of RSVP displays are manipulated. The results indicate that memory for specific text is facilitated when additional processing time is provided. However, how and where the additional time is distributed within a text, over broad limits, is not important. We use a method of text memory assessment that is not typically used in RSVP research and that is more sensitive to text presentation manipulations than the commonly used multiple-choice questions. This fill-in-the-blank technique also provides evidence that memory representations for texts are structured as meaningful subsentence units.

Effects of cuing on short-term retention of order information.

In two experiments, subjects recalled one of two letter sequences following a digit-filled retention interval. Recall performance was increased by precues informing subjects which letter sequence would be tested, and the cuing advantage remained throughout 60-digit retention intervals. No improvement was found, however, for cues occurring after the letters but before the digits. The cuing effects were attributed to encoding, not rehearsal, processes and were explained by a version of the Estes perturbation model, which included a long-term storage component and a fixed perturbation probability.

Letter detection: A window to unitization and other cognitive processes in reading text.

Experiments are reviewed that use the letter-detection task, in which subjects read text and circle target letters. Evidence is provided that the letter-detection task reveals the processing units used in reading text and is influenced as well by visual, phonetic, and a combination of semantic and syntactic factors. Specifically, it is shown that circling a target letter in a word depends on the familiarity of the word's visual configuration, the location of the word in the reader's visual field, the phonetic representation of the letter in the word, and a combination of the word's meaning and its grammatical function.

Searching for target letters in memory: Individual preferences and instructions for text representation.

Participants searched for target letters in a short passage held in memory. In Experiment 1, participants were divided into two groups on the basis of a retrospective report concerning the type of representation used to store the passage in memory, and in Experiment 2, participants were instructed concerning the form of memory representation to use. Only participants using a visual representation missed more targets in the wordthe than in other words. Participants instructed to form a visual representation also made fewer content-word or phrase substitutions when learning the passage than did participants instructed to form an auditory representation. These findings show that choice of memory representation is flexible and that the representation used influences what can be retrieved from memory.

Retention and transfer of morse code reception skill by novices: part-whole training.

The training of composite skills requiring differential responding to a large set of stimuli raises issues about how to break down the whole task into parts and which parts should be trained first. Components of Morse code reception skill were identified, separated, and used to test whether initial training on a difficult part was more effective than initial training on an easy part. Initial training on a difficult subset of stimuli and on a difficult subtask both yielded disadvantages rather than the advantage implied by recent findings with different tasks. Incremental training should begin with the part yielding the most effective strategic skills, which appear to depend on characteristics of the task. In both present experiments, easy initial training led to adoption of an effective unitization strategy for representing codes. The hypothesis that procedural reinstatement at delayed testing leads to better retention was supported and extended.

Identification of letters in the predesignated target paradigm: a word superiority effect for the common word the.

The size of the perceptual unit used in reading was addressed using the predesignated target paradigm. Sixteen subjects viewed the following stimuli in random order: the words tee, the, tie, and toe; the nonwords eet, eht, eit, and eot; and the letters e, h, i, and o. Subjects fixated on the location of the center letter and identified the letter as e, h, i, or o, alternatives which were known to them at the onset. A word superiority effect was obtained for the common word the but not for the less common words tee, tie, and toe. The word superiority effect was attributable to bias rather than discriminability: Subjects exhibited a bias to perceive the words in this experiment as the (i.e., there was a bias to perceive h in the t e stimulus presentations). These results suggest that the common word the is processed in reading units that are larger than the letter, and that the system is biased to perceive common rather than uncommon words in data-limited conditions.