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Delta9-tetrahydrocannabinol and pentobarbital as discriminative cues in the Mongolian Gerbil (Meriones unguiculatus)

Male Mongolian gerbils were trained to escape electric shocks in a T-shaped maze contingent upon the presence or absence of certain drug effects (state-dependency; StD). The drug discriminative cues used were those of either delta9-tetrahydrocannabinol (THC) or pentobarbital (P-barb.) vis-à-vis the respective vehicles. Several doses of THC (0.5-16.0 mg/kg) were used and compared with P-barb. (20.0 mg/kg), a dose at which the most rapid drug discrimination occurs in the rat. When drug discrimination was established dose-time- and transfer characteristics for the training drugs were studied. Possible potentiation and antagonism was also examined in the pentobarbital trained gerbils. It was found that none of the THC doses were discriminated as rapidly as that of P-barb. Decreasing the amounts of training drug administered or increasing the injection-test intervals resulted in a decline of the number of drug associated choices. There was a maximum of 40% drug choices between THC and P-barb at the transfer tests. Mixtures of the two compounds increased the number of drug choices in an additive or even more than additive manner. Amphetamine (4.0 mg/kg) did not interact with the P-barb. induced choice responding. The analeptic drug, bemegride was found effective in antagonizing the P-barb. cued choice behavior.

Amphetamine↗

Effects of piracetam on indices of cognitive function in a delayed alternation task in young and aged rats.

The effects of piracetam (64, 128, and 256 mg/kg PO) on the performance of a delayed alternation in a Skinner Box were investigated. Test sessions consisted of 36 trials during which animals were first presented with a single lever (left or right) followed 5, 10, or 20 s later by two levers. A press on the lever opposite to that presented previously (nonmatching to sample) was rewarded. The number of correct responses and the reaction times to the one- and two-lever presentations were recorded. All animals received all treatments in a balanced order. Aged animals showed clear deficits on all three parameters. Piracetam was without effect on the performance of young animals but dose-dependently decreased the choice reaction times (two levers) in aged animals without affecting the other two parameters. These results suggest that piracetam does not affect short-term memory but may facilitate choice behavior in aged animals.

Aging↗

Industrial lead poisoning in China over the past 33 years.

This paper is a review of the 48 articles in scientific journals and special reports of investigations emanating from the author's department involving 2504 subjects. During the past 33 years, as a result of the establishment of health and antiepidemic stations throughout the country, the enactment of hygienic standards, and the setting up of the reporting system for industrial poisoning and occupational diseases, the air lead level has been reduced from 10 mg/m3 in the years soon after liberation (1949) to below 0.03 mg/m3 at present. Severe plumbism has disappeared. Some mild cases, however, could still be found among workers in lead smelters and electric battery plants. Great advances have been made in techniques for early diagnosis of lead poisoning. Blood lead, urine lead, aminolevulinic dehydrase, free erythrocyte protoporphyrin, and zinc protoporphyrin (ZnPP) have been used as criteria for lead exposure. For the purpose of preventive monitoring, ZnPP as a screening index is the first choice. Behavioral function and sensory and motor nerve conduction velocity measurements of median nerve might also be used for the investigation of lead exposure. The maximum allowable concentration of 0.03 mg/m3 for air lead level in the workshop, in agreement with the results of a nationwide lead industry investigation, has been proven safe. There is also the need to monitor the air lead level and blood lead level in the general population and children living adjacent to a lead industry.

Adult↗

Heuristics or general learning processes?

The concept of heuristics implies that the rules governing choice behavior may vary with ecological constraints. Behavior analysis, in contrast, seeks general principles that transcend specific situations. To the extent that search is successful, the concept of heuristics is unlikely to play a significant role in the analysis of animal behavior.

Algorithms↗

The compulsion zone: a pharmacological theory of acquired cocaine self-administration.

In rats trained to reliably self-administer cocaine, the cumulative drug level was calculated during sessions in which cocaine was administered either contingently or non-contingently. During both types of sessions a high rate of responding was observed only when cocaine levels were above the priming threshold but below the satiety threshold. When the levels of non-contingently administered cocaine were maintained between the priming and satiety thresholds for at least 5 h rats continuously maintained high rates of responding. Although it is generally assumed that rats are responding for cocaine during self-administration sessions, the persistence of responding during non-contingent administration is consistent with responding being induced by cocaine. Therefore, in contrast to the basic assumptions underlying the operant theory of self-administration behavior, choice, contingency and reinforcement are not necessary to explain acquired cocaine self-administration. The presented data demonstrate that there is no ascending limb of the dose-response curve and that the cocaine priming and satiety thresholds delineate the lower and upper limits, respectively, of a cocaine "compulsion zone". It is concluded that the self-administration paradigm is the sum of cocaine induced responding and cocaine induced satiety and which of these cocaine-induced effects occur at any time is dependent on the cocaine level. This novel pharmacokinetic/pharmacodynamic theory provides a basis for a comprehensive understanding of the cocaine self-administration paradigm.

Animals↗

The neuroscience of investing: fMRI of the reward system.

Functional magnetic resonance imaging (fMRI) has proven a useful tool for observing neural BOLD signal changes during complex cognitive and emotional tasks. Yet the meaning and applicability of the fMRI data being gathered is still largely unknown. The brain's reward system underlies the fundamental neural processes of goal evaluation, preference formation, positive motivation, and choice behavior. fMRI technology allows researchers to dynamically visualize reward system processes. Experimenters can then correlate reward system BOLD activations with experimental behavior from carefully controlled experiments. In the SPAN lab at Stanford University, directed by Brian Knutson Ph.D., researchers have been using financial tasks during fMRI scanning to correlate emotion, behavior, and cognition with the reward system's fundamental neural activations. One goal of the SPAN lab is the development of predictive models of behavior. In this paper we extrapolate our fMRI results toward understanding and predicting individual behavior in the uncertain and high-risk environment of the financial markets. The financial market price anomalies of "value versus glamour" and "momentum" may be real-world examples of reward system activation biasing collective behavior. On the individual level, the investor's bias of overconfidence may similarly be related to reward system activation. We attempt to understand selected "irrational" investor behaviors and anomalous financial market price patterns through correlations with findings from fMRI research of the reward system.

Behavioral Sciences↗

Predictive neural coding of reward preference involves dissociable responses in human ventral midbrain and ventral striatum.

Food preferences are acquired through experience and can exert strong influence on choice behavior. In order to choose which food to consume, it is necessary to maintain a predictive representation of the subjective value of the associated food stimulus. Here, we explore the neural mechanisms by which such predictive representations are learned through classical conditioning. Human subjects were scanned using fMRI while learning associations between arbitrary visual stimuli and subsequent delivery of one of five different food flavors. Using a temporal difference algorithm to model learning, we found predictive responses in the ventral midbrain and a part of ventral striatum (ventral putamen) that were related directly to subjects' actual behavioral preferences. These brain structures demonstrated divergent response profiles, with the ventral midbrain showing a linear response profile with preference, and the ventral striatum a bivalent response. These results provide insight into the neural mechanisms underlying human preference behavior.

Adult↗

Withdrawal, tolerance, and sensitization to dopamine mediated interoceptive cues in rats trained on a three-lever drug-discrimination task.

In the present experiment rats were trained on a three-lever, drug-discrimination task to discriminate the cues associated with 0.30 mg/kg of the indirect dopamine (DA) agonist, amphetamine (AMPH), saline (SAL), and 0.03 mg/kg of the DA, D2 receptor antagonist, haloperidol (HAL). Choice behavior determined from tests on 0.30 and 0.15 mg/kg AMPH, SAL 0.03 and 0.015 mg/kg HAL provided a behavioral baseline presumed to represent changes along a continuum of DA mediated, interoceptive cues. Results from separate groups tested on 0.30 and 0.15 mg/kg AMPH, SAL, 0.03 and 0.015 mg/kg HAL, 24 h post-treatment with an acute 7.5 mg/kg dose of AMPH, showed rapid tolerance and withdrawal to the AMPH cue and sensitization to the HAL cue. The same tests 24 h following treatment with 1.0 mg/kg HAL showed rapid tolerance to the HAL cue, sensitization to the AMPH cue, but not AMPH-like withdrawal cues. Analysis of the results showed that tolerance to the AMPH and HAL cues reflected neuroadaptive baseline shifts and not weaker cue properties. These findings are consistent with predictions from opponent process theory of motivation and provide an animal model to study the motivational consequences that aversive symptoms of AMPH withdrawal such as dysphoria and anhedonia can have on drug-taking behavior.

Amphetamine↗

An analysis of Snoezelen equipment to reinforce persons with severe or profound mental retardation.

Systematically developing methods of reinforcement for persons with severe and profound mental retardation has only recently received a good deal of attention. This topic is important since professionals in the field often have difficulty identifying sufficient numbers of positive stimuli. Snoezelen equipment as reinforcement for individuals with severe and profound mental retardation was evaluated because of the promise it holds for this population. Types of Snoezelen equipment which were most often approached and most reinforcing for these persons were identified. Implications of the findings for future assessment and treatment are discussed.

Adult↗

An evaluation of a stimulus preference assessment of auditory stimuli for adolescents with developmental disabilities.

Previous researchers have used stimulus preference assessment (SPA) methods to identify salient reinforcers for individuals with developmental disabilities including tangible, leisure, edible and olfactory stimuli. In the present study, SPA procedures were used to identify potential auditory reinforcers and determine the reinforcement value of preferred and non-preferred auditory stimuli. The results from this study suggest that the paired stimulus procedure utilized was effective in identifying preferred and non-preferred auditory stimuli, as the contingent application of the identified auditory stimuli produced higher rates of correct responding than did non-preferred auditory stimuli for all participants.

Acoustic Stimulation↗

Effects of the beholder's age on the perception of facial attractiveness.

Children have been shown to prefer faces rated as highly attractive by adults over faces rated as quite unattractive. We investigated to what extent this agreement holds not only for the general direction of preferences but for preference strengths as well. In a choice experiment, we presented 40 nine-year-old girls and their mothers and 40 twelve-year-old girls and their mothers with pairs of women's and girls' faces and asked the subjects to pick the face that appeared prettier to them. Preference frequencies and simple attractiveness scales derived from these preference frequencies by fitting the Bradley-Terry-Luce rule (Luce, D. R. (1959). Individual choice behavior: a theoretical analysis. New York: Wiley) were compared across subject groups. For the women's faces, we found no difference in preferences between nine-year-olds, twelve-year-olds, and adults, neither in direction nor in strength. For the girls' faces, we also found no major differences in preference direction, however, we did find reliable differences in preference strengths. To a considerable part these differences were due to the fact that the children showed less pronounced preferences between face stimuli than the adults. These results suggest a role of developmental factors in the perception of facial attractiveness.

Adult↗

Pharmacologic treatment of childhood migraine.

This review of pharmacologic treatment of childhood migraine shows that no agent for abortive treatment has been proved effective in controlled studies and that most commonly used prophylactic agents (e.g., propranolol and cyproheptadine) lack proof of their effectiveness. Flunarizine seems to be the only agent with positive results in controlled studies. This drug, although well tolerated, is slow to act. For the treatment of an acute attack, aspirin or acetaminophen may be chosen. Two of us currently use propranolol as the first-choice prophylactic agent because of its tolerance and cost, and on the assumption of its effectiveness reported by the adult studies. For children with a history of asthma, metoprolol may be chosen because of its selective blocking of the beta 1-adrenoreceptor. One of us (W.N.M.) prefers cyproheptadine as the drug of choice. Behavioral therapy may be a good alternative to pharmacotherapy in the management of childhood migraine.

Child↗

Effects of intracerebroventricularly administered leptin on protein selection in the rat.

The effect of centrally administered rat leptin on selection of 5 and 30% protein diets was investigated in male Sprague-Dawley rats with indwelling i.c.v. cannulas. Leptin (0 vs 2.5 microg/day) was administered for 4 consecutive days, followed by an 8-day withdrawal period. Total intake was reduced to approximately 50% of that in the vehicle injected group during each day following leptin administration. Intake of both the 5 and 30% diets was reduced. Vehicle-treated rats selected a 13-15% CP diet. Diet selection in leptin-treated rats was not different during the first day, but on Days 2-4, leptin-treated rats selected a 10% CP diet. Intake began to normalize within 24-48 h after the last treatment, and was not different by Day 3 of the withdrawal period. Body weight was reduced by leptin treatment, and despite the normalization of food intake, did not recover during the withdrawal period. Rats were sacrificed at the end of the 8-day withdrawal period. Despite the reduction in body and carcass weights, liver, kidney, heart, and soleus muscle weights were not different between control and leptin-treated groups when expressed on an absolute or relative basis. However, epididymal and retroperitoneal fat pad weights were still reduced 56 and 78%, respectively, in rats that had been previously treated with leptin for 4 days and then not treated for 8 days. In addition, circulating T3 levels remained elevated in rats that had been treated with leptin. Centrally administered leptin has little effect on muscle mass, but had potent effects on intake of nonobese rats and a sustained effect on adipose tissue mass, thyroid hormone status, and body weight after withdrawal. Results from rats selecting between diets varying in protein content suggest that leptin may cause avoidance of protein.

Animals↗

Simultaneous color contrast in goldfish--a quantitative study.

A set of 9-15 colored test fields was presented to goldfish. In Experiment 1, test field hues ranged from green through yellow to red; in Experiment 2, the hues varied from blue through gray to yellow. In the training conditions, the test fields were presented with a gray or black surround. The fish learned to choose one intermediate test field hue by rewarding them with food. In the test conditions, the color of the surround was changed from gray to green, or red (Experiment 1), and from black to blue, or yellow (Experiment 2). The choice behavior of the goldfish changed substantially: one of the test fields other than the training test field was preferred. Direction and strength of simultaneous color contrast was quantified in goldfish color space. The effect of spatial stimulus configuration was investigated by changing test field size and using narrow annular surrounds. With test field radii ranging between 2 and 7.5 mm simultaneous color contrast was optimal whenever the ratio between surround width and test field radius had a value of about 1:1.

Algorithms↗

Effects of sodium azide on motor activity, motor coordination, and learning.

Because of the proposed importance of cytochrome oxidase in some neurological disorders, an inhibitor of this enzyme was evaluated in a battery of tests measuring exploration, motor coordination, and learning. Mice injected with sodium azide (6 or 12 mg/kg) were slower to initiate a response in a T maze and had less rears in a small chamber than mice injected with placebo. Drugged mice did not alternate spontaneously even at a minimal retention interval (0 min), but were not impaired in water maze spatial and visual discrimination learning tasks. No group differences emerged in terms of horizontal motor activity and its habituation, number of grooming episodes, and motor coordination. These results indicate that azide-induced slowing of motor activity is situation-specific and is accompanied by abnormalities in choice behavior in a T maze.

Animals↗

Cumulative vs. acute dose-response procedures produce differential BAC and behavioral functions for ethanol.

The discriminative stimulus attributes of ethanol (ETOH) were characterized in rats trained to discriminate between 1.25 g/kg ETOH and saline. The ETOH generalization functions were assessed using both acute and cumulative dosing procedures. The cumulative procedures differed in the individual incremented doses used to generate the functions. Acute dosing procedures produced discriminative functions that were significantly different from cumulative dose-response curves (DRCs). Similar cumulative DRC's were generated within each cumulative dosing procedure, whereas significant differences were produced between the two dosing incremented procedures. When blood alcohol concentrations (BACs) were quantified, a cumulative testing procedure produced significantly lower BACs than acute testing procedures at every dose above the initial or starting dose. Interestingly, response rate functions did not differ within or between cumulative and acute procedures. These data may suggest that differential ETOH dosing procedures may differentially influence the behavioral choice and BAC functions in rats, and cautions against the use of cumulative procedures to assess shifts in DRCs during chronic treatments without a concomitant assessment of BACs.

Animals↗

The effects of d-amphetamine on intake of food and a sweet fluid containing cocaine.

Using a laboratory animal procedure designed to measure two aspects of reinforcement (self-administration and location preference), five adult rhesus monkeys each lived in three chambers: oral cocaine self-administration (0.26 mg/kg/delivery cocaine hydrochloride in a sweet fluid) was specific to one end chamber, food self-administration was specific to the other end chamber, and no food cues or fluid cues were available in the middle chamber. Throughout the 10-h experimental day monkeys experienced multiple food, cocaine, and choice (food vs. sweet cocaine fluid), sessions. Oral d-amphetamine (AMPH; 0.5-1.5 mg/kg) or placebo was administered before the sessions to determine if this anorectic drug would differentially alter food and sweet cocaine fluid self-administration. Further, the effects of AMPH on the length of time a monkey spent in each chamber, when the stimulus cues indicating commodity availability were not present (location preference) were determined. AMPH produced dose-dependent decreases in both food and cocaine self-administration without affecting choice behavior. AMPH also increased the length of time monkeys spent in the food chamber, even when no stimuli indicating food availability were present. These results indicate that the relationship between self-administration and location preference measures of reinforcement is not completely concordant. The current procedure may prove useful in studying these two measures of reinforcement.

Animals↗