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Preclinical effects: learned behavior.

A review of the previous Marihuana and Health Reports (1971-1975) reveals that an extensive array of experimental procedures and contexts have been used to study the effects of cannabinoids on the performance of learned behavior in animals. These preclinical behavioral experiments have provided a framework for, and guided the design of, subsequent human experimentation. Compared to previous years, only a few experiments pertaining to cannabinoids and learned behavior have appeared during the past two years. By and large these more recent experiments confirm previous findings; no particularly novel procedures have been explored nor have there been dramatically unpredictable results. In part, the decrease in activity in cannabinoid preclinical animal research on learned behavior indicates an increase in human cannabinoid-learning investigations. Several detailed taxonomies of learned behavior are possible. However, for the purposes of the present report, learned behaviors will be categorized into those involving: avoidance learning and aversive control; reinforcement schedules and maze learning; and discrimination learning.

Animals↗

Inactivation of dorsolateral striatum enhances sensitivity to changes in the action-outcome contingency in instrumental conditioning.

Actions become compulsive when they are no longer controlled by their consequences. Compulsivity can be assessed using the omission procedure in which animals are required to withhold a previously reinforced action to earn reward. The current study tested the hypothesis that inactivation of the dorsolateral striatum (DLS), a structure implicated in habitual behavior, can enhance sensitivity to changes in the action-outcome contingency during omission training, thus leading to a reduction in compulsive responding. Over 10 days rats were trained to press a freely available lever for sucrose reward delivered on interval schedules of reinforcement. After learning to press the lever at a stable and high rate, rats in the omission group received a session in which the rewards were now delayed by pressing the lever; i.e. withholding lever pressing resulted in increased access to reward. A control group was yoked to the omission group and received the same number and pattern of reward delivery but without the omission contingency. Half the rats in each group received infusions of vehicle into the DLS prior to this training whereas the remainder received an infusion of the GABA-A receptor agonist muscimol. On the next day, the effect of these treatments was assessed on a probe test in which the tendency of the various groups to press the lever was assessed in extinction and without drug infusion. Rats that received vehicle infusions prior to the omission session showed complete insensitivity to the newly imposed omission contingency. In contrast, rats given the infusion of muscimol selectively reduced lever pressing compared to yoked controls. Thus, extended training with interval schedules resulted in compulsive lever pressing that prevented the learning of the omission contingency, whereas inactivation of the DLS appeared to enhance the rats' sensitivity to this change in the action-outcome contingency.

Analysis of Variance↗

Continuing Medical Education in Clinical Pharmacology and Therapeutics: report of a questionnaire survey.

AIMS: To seek the views of medically qualified members of the Clinical Section of the British Pharmacological Society (BPS) on their perceived needs for Continuing Medical Education (CME); on how and by whom these needs should be addressed; and on how the outcome of any educational intervention might best be assessed. METHODS: A structured questionnaire. RESULTS: Of 233 recipients, 140 (60%) responded, but only 123 of these fulfilled the criteria for analysis. A large majority of respondents were clinicians, most of whom devoted at least 25% of their working week to their NHS commitment. There was widespread reliance on textbooks and journals as sources of CME, supplemented by discussions with specialist peers at national and international meetings. Many felt that fulfilling even this agenda was stretching their commitment to the limit, and their greatest need was for protected time in which to learn. There was a desire among 49% of all respondents for the BPS Clinical Section to take some responsibilty for addressing the future needs of its members, and 75% took the view that academic departments should contribute to the development and updating of materials. There was no clear agreement about what these should comprise, but around half of all respondents favoured web-based, journal-based or computer-assisted educational material offering self-assessment opportunities; and CME symposia or workshops at BPS meetings. Almost half (46%) felt that assessment of CME should be integrated with a well-organized appraisal system and the use of portfolios. Six out of 10 respondents were already, or were about to be, regularly appraised at their place of work. CONCLUSIONS: The questionnaire survey revealed a broad canvas of views and little evidence of consensus except for a general plea for more time in which to learn. The aim of the Clinical Section should be to facilitate and help its members to organize their learning, in a way that is consistent with national trends in Continuing Professional Development. The Clinical Section should co-ordinate the setting up of an electronic library of appropriate published material, compiled by academic and industrial sources, that would guide members seeking up-to-date knowledge of Clinical Pharmacology and Therapeutics. The British Journal of Clinical Pharmacology (BJCP) should commission review articles on recent developments where no suitable published material exists. Academic departments should also be invited to identify or develop self-assessment material that members could use to reinforce their learning, and demonstrate their knowledge to relevant professional bodies. The Clinical Section should organize Symposia and Workshops at which contentious issues in Clinical Pharmacology and Therapeutics can be discussed and resolved.

Education, Medical, Continuing↗

Selective word-learning deficits in aphasia.

The purpose of this study was to determine whether patients with focal brain damage can learn anything about a new word, and if so, whether selected aspects of the new word are acquired depending on the nature of the patient's language processing deficit. In the context of drawing pictures with a number of felt pens identical in all respects except color, agrammatic Broca's aphasics and fluent aphasics were exposed to the new word "bice," an adjective referring to the dark green portion of the color spectrum. Our findings revealed that brain-damaged patients can engage in lexical acquisition, but Broca's aphasics and fluent aphasics apparently learn about different aspects of the new word. Specifically, on successive exposures to "bice," both Broca's aphasics and fluent aphasics exhibit progressively more accurate hypotheses for identifying a bice-colored object. During subsequent assessments, agrammatic aphasics reveal on a metalinguistic judgment task their significant difficulty appreciating the grammatical form class of "bice"; on an object classification task, fluent aphasics are significantly impaired in their classification of bice-colored objects as "bice." Taken together, these unique word-learning profiles reinforce earlier observation on the selective nature of language processing deficits after focal left-hemisphere insult, and support the claim that separate language processing devices may be selectively compromised in different groups of aphasics. The relationship between syntactic and lexical semantic processing is discussed.

Adult↗

Effects of chlorpromazine on appetitive and aversive components of a multiple schedule.

A multiple schedule having both an appetitive and an avoidance component was maintained in two dogs to create a complex behavioral base line for observing the effects of chlorpromazine. Both soluble and "Spansule" chlorpromazine generated similar functions relating drug dose to measures of behavioral output. Although the dose ranges and the drugging procedures differed markedly for the different preparations of CPZ, the functions generated were comparable. There was no evidence that chlorpromazine had a differential depressing effect as a function of type of reinforcement. At low doses, rates of responding on the food-reinforced components increased slightly, whereas rates on the avoidance components remained relatively unchanged. At higher doses, both components showed an approximately equal depression of responding. These results are discussed with reference to some of the logical and experimental difficulties inherent in making comparisons across components of a multiple schedule and across schedules in general.

Animals↗

The behavior of ants in a maze in response to a change from food motivation to protective motivation.

The ability of Myrmica rubra scout ants to modify the foraging habit, formed in a symmetrical multiple-choice maze, in the situation in which the reinforcement (syrup) was replaced with a brood of the same species was studied. When the "test" was performed at the same high level of food motivation of the family as applied during training, the ants were able successfully to transfer to another type of social behavior - transporting of the brood. When the high-level food motivation was replaced with a low-level motivation, some of the ants were unable to modify the habit. Preliminary utilization in these conditions of reinforcement as a switching factor addressing the motivational system for protective behavior promoted successful performance of the "test." Criteria allowing identification of different methods of modifying behavior during the switch from food motivation to protective motivation were developed. A total of 37.5% of the ants transferred the strategy formed during training: 40.6% showed gradual remodeling. while 21.9% of individuals immediately used the new strategy.

Animals↗

Temporal control on interval schedules: what determines the postreinforcement pause?

On fixed-interval or response-initiated delay schedules of reinforcement, the average pause following food presentation is proportional to the interfood interval. Moreover, when a number of intervals of different durations occur in a programmed cyclic series, postreinforcement pauses track the changes in interval value. What controls the duration of postreinforcement pauses under these conditions? Staddon, Wynne, and Higa (1991), in their linear waiting model, propose control by the preceding interfood interval. Another possibility is that delay to reinforcement, signaled by a key peck and/or stimulus change, determines the subsequent pause. The experiments reported here examined the role of these two possible time markers by studying the performance of pigeons under a chained cyclic fixed-interval procedure. The data support the linear waiting model, but suggest that more than the immediately preceding interfood interval plays a role in temporal control.

Animals↗

Psychophysiological evidence for impaired reward anticipation in Parkinson's disease.

OBJECTIVE: According to a widely held view, mesencephalic dopamine neurons mediate feedback-based learning by broadcasting an error signal that indexes the difference between anticipated and actual response-contingent reward. The present experiment tested whether impaired learning of a probabilistic classification task by individuals with Parkinson's disease (PD) is associated with abnormal reward expectation. METHODS: The stimulus-preceding negativity (SPN), a brain potential known to reflect anticipation of motivationally significant events, was compared for blocks in which subjects anticipated high or low monetary rewards and punishments. RESULTS: The SPN was reduced in amplitude in patients relative to controls in the high monetary incentive condition. Furthermore, whereas the SPN varied in size as a function of cue complexity for control subjects, it did not for patients. CONCLUSIONS: These results suggest that anticipatory processes within cortical portions of the reward system are impaired by PD. SIGNIFICANCE: These data support previous claims that the SPN offers an electrophysiological index of activity within cortical portions of the reward pathway, and that reinforcement-based learning is impaired in PD.

Aged↗

Reward-based decision-making and aging.

Healthy aging is associated with a number of neuroanatomical and neurobiological alterations that result in various cognitive changes. Both, the dopaminergic as well as the serotonergic system are subject to change during aging. Receptor loss and severe structural changes in PFC and striatum have been reported. Aging is associated with a progressive decline in several cognitive functions, such as episodic memory, working memory, and processing speed. Furthermore, it is associated with deficits in tasks requiring adaptation to external feedback of right or wrong, or task-switching. Here, we develop the hypothesis that this loss of behavioral flexibility is caused by structural and functional alterations of the reward system leading to impairments in reward processing, learning stimulus reinforcement associations, and reward-based decision-making. We review (a) data on neural correlates and substrates of reward processing in young healthy animals and humans, (b) evidence for age related functional and structural alterations of the reward system, and (c) behavioral and neuroimaging data of age effects on reward-based decision-making processes. Implications for neuroeconomics and neurodegenerative diseases are discussed.

Aging↗

Chlordiazepoxide impairs the performance of a learned discrimination.

Chlordiazepoxide (CDP) (5 mg/kg) administered on four of eight sessions significantly impaired the performance of a previously learned, reinforcement-cued discrimination in male Sprague-Dawley rats. On four interspersed vehicle-injection sessions, the performance of subjects demonstrated immediate recovery and was indistinguishable from that of controls (0 mg/kg). An analysis of response components indicated that the impairment in discrimination performance was due to a "disinhibitory" effect of the drug on responding during "no-go" phases of the task. The results are discussed in the context of similarities and differences in the effect of CDP on performance and acquisition.

Animals↗

Discriminated interresponse times: role of autoshaped responses.

When discriminated interresponse-time (IRT) procedures have been used to assess preference relations among temporally extended operants, deviations from matching have been obtained. Using a yoked-control procedure, the present study found that key pecking in a discriminated IRT procedure has two sources of strength--that arising from the response-reinforcer contingency that is explicitly arranged, and that arising from a stimulus-reinforcer contingency that is a by-product of the explicitly arranged contingency. The key pecking of all lead birds, and that of 3 of the 4 birds exposed to a yoked autoshaping procedure, was controlled by the keylight that signaled the lead birds' criterion IRTs. Because stimulus control of key pecking by the keylight, whether autoshaped or discriminative, fosters deviations from matching, the discriminated IRT procedure does not provide an appropriate basis for conclusions about preference relations among IRTs.

Animals↗

Perseverative behavior underlying attentional set-shifting deficits in rats chronically treated with the neurotoxin 3-nitropropionic acid.

Huntington's disease (HD) is generally considered a prototypic motor disorder, but cognitive deficits are also prominent features of the disease. Systemic administration of the mitochondrial toxin 3-nitropropionic acid (3NP) has been proposed to be a phenotypic model of HD in rats and nonhuman primates. In this study, we investigated the effect of 5 days continuous subcutaneous infusion of 3NP on motor and cognitive abilities in Lewis rats. Intoxicated animals developed a motor syndrome consisting of bradykinesia as well as gait abnormalities and dystonic hindlimbs. Results from learning tasks showed that these rats: (1) did not exhibit learning deficits per se in our discrimination task but showed impairments in inhibiting behavioral responses when a transfer of learning (to new stimuli) or a transfer of response (new position of the lever) was required; (2) showed a marked tendency to persevere in choosing the compartment they previously visited in a T maze, thus leading to a clear retardation in learning a reinforced alternation task; and (3) did not show any memory deficit when a delay was introduced. Six months later, histological analyses showed severe neurodegeneration within the lateral striatum accompanied by apparent cell loss in the ventral pallidum and entopedoncular nucleus. We suggest that the 3NP rat model of basal ganglia neurodegeneration may provide a useful model for studying certain fundamental aspects of the physiopathology of HD and for evaluating the functional efficacy of new therapeutic strategies.

Animals↗

Limbic corticostriatal systems and delayed reinforcement.

Impulsive choice, one aspect of impulsivity, is characterized by an abnormally high preference for small, immediate rewards over larger delayed rewards, and can be a feature of adolescence, but also attention-deficit/hyperactivity disorder (ADHD), addiction, and other neuropsychiatric disorders. Both the serotonin and dopamine neuromodulator systems are implicated in impulsivity; manipulations of these systems affect animal models of impulsive choice, though these effects may depend on the receptor subtype and whether or not the reward is signaled. These systems project to limbic cortical and striatal structures shown to be abnormal in animal models of ADHD. Damage to the nucleus accumbens core (AcbC) causes rats to exhibit impulsive choice. These rats are also hyperactive, but are unimpaired in tests of visuospatial attention; they may therefore represent an animal model of the hyperactive-impulsive subtype of ADHD. Lesions to the anterior cingulate or medial prefrontal cortex, two afferents to the AcbC, do not induce impulsive choice, but lesions of the basolateral amygdala do, while lesions to the orbitofrontal cortex have had opposite effects in different tasks measuring impulsive choice. In theory, impulsive choice may emerge as a result of abnormal processing of the magnitude of rewards, or as a result of a deficit in the effects of delayed reinforcement. Recent evidence suggests that AcbC-lesioned rats perceive reward magnitude normally, but exhibit a selective deficit in learning instrumental responses using delayed reinforcement, suggesting that the AcbC is a reinforcement learning system that mediates the effects of delayed rewards.

Adolescent↗

Trial order and retention interval in human predictive judgment.

The influences of order of trial type and retention interval on human predictive judgments were assessed for a cue that was reinforced on half of its training presentations. Subjects observed 10 cue-outcome presentations (i.e., reinforced trials) and 10 cue-alone presentations (i.e., nonreinforced trials) in one of three different orders: all nonreinforced trials followed by all reinforced trials(latent inhibition), reinforced and nonreinforced trials interspersed (partial reinforcement), or al lreinforced trials followed by all nonreinforced trials (extinction). Ratings were based mainly on the most recent event type (i.e., a recency effect) when the test occurred immediately after training but were based mainly on initial event types (i.e., a primacy effect) when the test occurred after a 48-h delay. The subjects tested both immediately and with a long retention interval did not exhibit this shift to primacy (i.e., the recency effect persisted). These results demonstrate noncatastrophic forgetting and the flexible use of trial order information in predictive judgments.

Adult↗

Choice with uncertain outcomes: conditioned reinforcement effects.

Pigeons responded on concurrent chains with equal initial- and terminal-link durations. In all conditions, the terminal links of one chain ended reliably in reinforcement; the terminal links on the alternative chain ended in either food or blackout. In Experiment 1, the terminal-link stimuli were correlated with (signaled) the outcome, and the durations of the initial and terminal links were varied across conditions. Preference did not vary systematically across conditions. In Experiment 2, terminal-link durations were varied under different stimulus conditions. The initial links were variable-interval 80-s schedules. Preference for the reliable alternative was generally higher in unsignaled than in signaled conditions. Preference increased with terminal-link durations only in the unsignaled conditions. There were no consistent differences between conditions with and without a common signal for reinforcement on the two chains. In the first series of conditions in Experiment 3, a single response was required in the initial links, and the stimulus conditions during 50-s terminal links were varied. Preference for the reliable outcome approached 1.0 in unsignaled conditions and was considerably lower (below .50 for 3 of 5 subjects) in signaled conditions. In a final series of signaled conditions with relatively long terminal links, preference varied with duration of the initial links. The results extend previous findings and are discussed in terms of the delay reduction signaled by terminal-link stimuli.

Animals↗

Faculty behavior: appraisal and rewards.

Faculty A & R systems arrange contingencies of reinforcement (relationships between faculty performance and institutional rewards) which powerfully influence faculty behavior. By and large, the current contingencies influencing teaching performance are defectiive. A frequent result is mediocre instruction and ready diversion of faculty effort to activities controlled by better contingencies. The major obstacles to productive appraisal and reward of teaching are the criterion problem and the inability or reluctance to arrange potent A & R contigencies to influence faculty behavior. Recent developments in behavioral science and instructional technology promise significant help in overcoming both obstacles. An example has been provided. Virtues and difficulties in the proposed procedure have been discussed.

Avoidance Learning↗

Students online: learning medical genetics.

It is possible to focus medical genetics education by using a model that integrates the skills of end-user searching of the medical literature into the traditional course content. Since 1988, 313 first-year medical students were studied as they accessed MEDLINE to retrieve information about biochemical genetic disorders. Their search behavior was studied by analyzing data from the National Library of Medicine's traffic files. The skills that they initially learned were reinforced as they searched clinical genetics problem cases in the second-year pathology course, and these skills were consolidated in the third year when the students addressed specific patient-care questions in pediatrics. The students' perception of the value of this model was studied by analyzing questionnaires completed during the exercise. It was demonstrated that when students were taught the skills of accessing MEDLINE by computer, they could formulate a question, retrieve current information, critically review relevant articles, communicate effectively, and use these skills to contribute to patient care.

Female↗