The effect of cocaine and D-amphetamine on punished responding

Various dosages of d-amphetamine (0.1, 0.5, 2.5 mg/kg) and of cocaine (5.0, 20, 40 mg/kg) were administered i.p. to each of 7 rats trained in an experimentally induced conflict procedure. Sessions were 1 hr in duration and consisted of five 12 min periods; responding was reinforced with food on a F124 sec schedule of reinforcement during each period; however, in periods 2 and 4 each response was followed by the application of footshock. Significant increase in responding did not occur in any period following any of the pretreatments. Cocaine (5.0, 20 mg/kg) and d-amphetamine (0.5, 2.5 mg/kg) significantly decreased responding in both punished and unpunished periods. Following these treatments the rate of responding in punished and unpunished components was not significantly different. This suggest that psychomotor stimulants may not selectively increase anxiety, at least at dosages which are not at the same time anorexic.     

Comparison of chlordiazepoxide and food deprivation on punished and unpunished responding maintained by food.

Twelve adult rats pressed a lever in daily 1-hr sessions on a modified Geller-Seifter conflict schedule to earn a 45-mg food pellet every 2 min on the average in one component and a pellet accompanied by an incremental footshock for every response in the other component (multiple variable-interval 2-min [food] fixed ratio (FR) 1 [food plus shock]). Body weight (M?=?322 g) and baseline responding were maintained by restricting postsession food to 1 hr. Chlordiazepoxide 25 mg/kg po raised shock-suppressed responding by 79% over baseline. Omitting postsession food for 5 days reduced mean body weight by 10% and raised variable interval (VI) responding by 137% but raised shock-suppressed responding by only 25%. Results suggest that the ability of conventional anxiolytics to raise shock-suppressed responding is therapeutic-class-specific and is not based on appetite enhancement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relationship between radiation doses and their effects

Dose-effect relationships have been developed both for the biological effects studied by Radiobiology and the long-term pathological effects (malignant diseases) studied by Radiation Protection. The former approach chiefly considers the primary biological injuries at the cellular level, and the relationship between the dependent variable characteristic of the effect and the dose--an independent variable--has an explanatory meaning. The parameters associated to the independent variable have a biophysical signification and fit into a model of the action of ionizing radiations. In the latter approach, the relationship is pragmatic and the previous parameters are just the result of a curve-fitting procedure realized on experimental or human data. The biophysical models have led to a general formulation associating a linear term to a quadratic term both of them weighted by an exponential term describing cellular killing at the highest doses. To a certain extent the curves obtained for leukemias, bronchopulmonary and breast cancers prove the validity of the pragmatic model.     

Overshadowing in landmark learning: Touch-screen studies with pigeons and humans.

Overshadowing in landmark learning was studied in pigeons and undergraduates using a touch-screen spatial search task. Ss searched for an unmarked goal presented in varied locations on a computer screen. Graphic stimuli served as landmarks. The effect of the presence of other landmarks on the control acquired by a given landmark was assessed using a design in which each S was trained with 2 sets of landmarks. Both pigeons (Experiment 1) and humans (Experiments 2–4) showed evidence of learning more about a landmark that was the closest landmark of its set to the goal than about a landmark that was of equal distance to the goal but was not the closest landmark of its set. That is, control by a landmark was overshadowed when it occurred together with a landmark that was closer to the goal. Landmark effectiveness appears to depend not only on the absolute properties of a landmark but on relative factors. The relevance of basic principles of associative learning to spatial landmark learning is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A clinical trial of escalating doses of flumazenil for reversal of suspected benzodiazepine overdose in the emergency department

STUDY OBJECTIVE: To determine if flumazenil, when used in doses higher than those currently recommended, could reverse the effects of a benzodiazepine (BDZ) overdose in patients who might not otherwise respond and whether the higher dose was associated with increased adverse effects. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, balanced, with parallel groups. Open-label flumazenil administration was available if a patient failed to respond or became resedated. SETTING: Sixteen emergency departments in the United States. POPULATION: Patients presenting to the ED with clinically significant signs and symptoms of a known or suspected BDZ overdose. INTERVENTIONS: Patients were randomized to receive 10 mL/min of placebo or flumazenil (1 mg/10 mL) each minute for ten minutes. If there was no response, up to 3 mg of open-label flumazenil could be administered. MEASUREMENTS AND MAIN RESULTS: Of 170 patients enrolled, 87 received flumazenil and 83 received placebo. The demographic characteristics of both groups were comparable. Ten minutes after the beginning of study drug infusion, patients were evaluated using the Clinical Global Impression Scale (CGIS), Glasgow Coma Scale (GSC), and Neurobehavioral Assessment Scale (NAS). The mean +/- SD CGIS score at ten minutes for BDZ-positive patients was 1.41 +/- 0.72 for patients who received flumazenil and 3.41 +/- 0.91 for the placebo group (P < .01). There was no difference in the mean CGIS score between the flumazenil (3.25 +/- 1.15) and placebo (3.75 +/- 0.69) groups in BDZ-negative patients. The GCS and NAS were also significantly better in patients who were BDZ-positive and received flumazenil. The mean +/- SD dose of flumazenil administered during the double-blind phase was 71.3 +/- 34.2 mL (7.13 mg) compared with 95.06 +/- 16.03 mL of placebo. Of the 39 patients who had BDZ-positive drug screens and received flumazenil, 29 (74%) responded to 3 mg or less. Six additional patients responded to 4 or 5 mg, and one patient responded to 8 mg. The most common adverse effects in patients who received flumazenil were injection site pain (10.3%), agitation (8%), vomiting (3.4%), dizziness (3.4%), headache (3.4%), tachycardia (3.4%), and crying (3.4%). Three patients developed seizures. Two were associated with significant tricyclic antidepressant overdoses and one with propoxyphene ingestion. Two patients had positive drug screens for BDZ. CONCLUSION: Flumazenil rapidly and effectively reverses the clinical signs and symptoms of a BDZ overdose. Most patients will respond to 3 mg or less, but a small number may require a higher dose for reversal of clinical symptoms. Patients with concomitant tricyclic antidepressant overdose may be at risk for developing seizures.     

Distributions of GABAA, GABAB, and benzodiazepine receptors in the forebrain and midbrain of pigeons

The single-stranded DNA parvoviruses occur in humans and many species of animals. In general, they are species-specific and capable of producing disease at any stage of life. Parvoviruses have a requirement to replicate in cells in a permissive S-phase of DNA mitosis. The infections may be cytolytic to select cell groups resulting in specific developmental defects or may produce more generalized effects such as anemia, pancytopenia, or hemorrhage. The fetus is at particular risk for damage because of the vast number of cells in active mitosis. The teratogenic effects may be severe, often resulting in fetal death. Infections in childhood and adulthood are more frequently mild to subclinical. Some of the teratogenic effects recognized in animal species have been identified in humans. With increased knowledge of parvovirus effects in animals, more pathogenic effects may be related to human parvoviral disease. The need for vaccination, currently used annually in many domestic animal species, continues to be evaluated for humans.     

Effects of physostigmine on benzodiazepine toxicity

The interactions between physostigmine and chlordiazepoxide, diazepam, flurazepam were experimentally evaluated in rats and mice by the following test: loss of righting reflex (LRR), acute toxicity, cardiovascular toxicity and EEG pattern. Physostigmine did not modify the duration of LRR produced by chlordiazepoxide. Conversely, the recovery after diazepam was significantly longer. The LD50 of diazepam and chlordiazepoxide were not modified by physostigmine administration, but that of flurazepam was significantly decreased. Heart rate and blood pressure did not change significantly with physostigmine pre-treatment. However, the total lethal dose was lowered for chlordiazepoxide and flurazepam. Only the reversal by physostigmine of the EEG pattern due to benzodiazepines, offers experimental support to the claimed usefulness of physostigmine in benzodiazepine intoxication in humans. Furthermore, the potentiation of flurazepam toxicity must be taken into account in the debate concerning the clinical advantages of physostigmine.     

Discrimination of letters and random dot patterns by pigeons and humans.

Conducted 2 exploratory experiments to compare pigeon and human perception of visual stimuli. In a 3-choice discrimination task, 3 white Carneaux pigeons learned to distinguish each letter of the alphabet from all the other letters and each of 16 random dot patterns from all the others, and Ss' discrimination errors were used to generate a matrix of interletter and interpattern similarities. Human estimates of letter similarity were obtained from previous literature, and 6 human adults rated the similarity of the dot patterns. Performances of the humans and of 6 pigeons were described and compared through correlation, multidimensional scaling, and cluster analysis, and fits of the data by simple-feature and template models were computed and compared. The correlation between pigeon and human similarity matrices was .68 for letters and .72 for dot patterns. The other analyses revealed broadly similar patterns of results from the 2 species but suggested that, relative to human data, the best fits to the pigeon data required fewer dimensions, fewer features, and fuzzier templates. There was some indication that pigeon discriminations depended on relatively simple features, and several of these were tentatively identified. It is suggested that the different methods employed could have influenced these apparent differences between pigeons and humans, but, overall, findings suggest considerable cross-task and cross-species generality in the processing of these simple forms. (47 ref) (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Effects of naltrexone on response to intravenous cocaine, hydromorphone and their combination in humans

This study evaluated the effects of i.v. cocaine, hydromorphone and their combination, and assessed the ability of oral naltrexone, an opioid antagonist, to modulate these effects. Volunteers with cocaine and heroin abuse histories (n = 8) participated in this placebo-controlled, cross-over study while residing on a closed research unit. Daily treatment with capsules containing placebo or naltrexone in ascending doses (3.125, 12.5, 50 and 200 mg) were given for 7-day periods. In thrice weekly experimental sessions, cocaine, hydromorphone and their combination were given in random order. Drug doses were given in an ascending order 1 hr apart as follows: cocaine at 0,20 and 40 mg, hydromorphone at 0, 1.5 and 3.0 mg, and the combination of 0 and 0 mg, 20 mg cocaine and 1.5 mg hydromorphone and 40 mg cocaine and 3.0 mg hydromorphone. Hydromorphone and cocaine produced distinct pharmacodynamic profiles, and the combination produced effects similar to both drugs. In some cases, the magnitude of effects produced by the combination was greater than that produced by either drug alone. Naltrexone produced dose-related blockade of hydromorphone effects, but did not after any of the physiological or subjective effects of cocaine. All naltrexone doses partially attenuated the effects of the combination and this appeared to be attributable to selective opioid blockade. These data do not support the use of naltrexone as a treatment for cocaine abuse, but suggest it may be useful for treating patients with concurrent cocaine and heroin abuse.     

Altered responding to cholecystokinins and dopaminergic agonists following 6-hydroxydopamine treatment in rats.

In 5 experiments with 265 male Wistar albino rats, production of lesions in the brain dopamine (DA) system by intraventricular injection of 6-hydroxydopamine (6-OHDA) resulted in increased responses to subcutaneous apomorphine (0.5 mg/kg) and reduced responses to methamphetamine (0.15 mg/kg). It also made Ss increase responding to intracerebroventricular (icv) cholecystokinin octapeptide (CCK-8; 0.5–2 μg) and reduce responding to cholecystokinin tetrapeptide (CCK-4; 0.5–2 μg). Response changes were quantified by measuring the level of general activity. Results indicate that DA dysfunction not only affected DA receptor sensitivity but also the sensitivity of the CCK system. The response to CCK-8 was partially blocked by a selective CCK-8 antagonist, proglumide (5 μg, icv), a result suggesting the involvement of the CCK-8 receptor system. Results indicate that manipulation of 1 neuronal system could induce sensitivity changes in another closely related system. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of exposure to a punished model and verbal prohibitions on children's toy play.

Studied the effects of exposure to a punished model on children's toy play. 72 of 108 kindergartners and 1st graders in the sample watched a videotape of a girl model punished for touching toys. In prior research, punishment of a model was confounded with verbal prohibitions; in the present study, the problem was controlled by giving 3 levels of prohibition: strong, mild, or none. Seeing a model punished significantly inhibited the Ss, but this effect was masked with Ss who received strong prohibitions. Ss who saw the videotape maintained their inhibitions over time and generalized them to an unfamiliar adult. Kindergartners who received only strong prohibitions did not remain inhibited over time. It is concluded that viewing social consequences to others can play a significant role in the socialization of children. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of methylphenidate on cooperative responding in children with attention deficit-hyperactivity disorder.

The effects of methylphenidate on cooperative responding in children with attention deficit hyperactivity disorder were examined. During 1 of 2 alternating periods of a laboratory task, the child's button presses added points to a counter marked Your Earnings. During the 2nd period, cooperative and independent response options were available. Cooperative responses added points simultaneously to a counter marked Your Earnings and Other's Earnings. Concurrently available independent responses added points only to the counter marked Your Earnings. Time allocated to the cooperative response option was significantly decreased following acute administration of the 0.3 mg/kg and the 0.6 mg/kg methylphenidate doses as compared with placebo. Implications for understanding the behavioral mechanism of methylphenidate effects on social behavior are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of carbon disulfide and FLA-63 on operant behavior in pigeons

Carbon disulfide (CS2) and FLA-63 [bis(4-methyl-1-homopiperazinylthiocarbonyl)disulfide] were studied in pigeons working on a differential-reinforcement-of low-rates or a multiple fixed-interval fixed-ratio schedule of food reinforcement. Response rate on both schedules decreased after 8-hour exposures to CS2 (2 mg/1) of administration of FLA-63 (40 and 80 mg/kg). The effects of two successive 8-hour exposures to CS2 were cumulative and ten successive 4-hour exposures produced changes in differential-reinforcement-of-low-rates performance resembling those following acute exposure. Fixed-interval performance was disrupted by exposures to CS2 and doses of FLA-63 that left fixed-ratio performance intact.     

Role of differential sample responding in the differential outcomes effect involving delayed matching by pigeons.

The role of differential sample responding in the differential outcomes effect was examined. In Exp 1, pigeons were trained on a one-to-many matching task with differential sample responding required. Differential outcomes were associated with samples and comparisons, with comparisons only, or with neither samples nor comparisons. Slopes of delay functions for trials with pecked versus nonpecked samples suggested use of a single-code-default strategy in the nondifferential-outcomes group but not in the differential-outcomes groups. In Exp 2, differential sample responding and differential outcomes were manipulated independently. Again, there were significant differences in the relative slopes of the delay functions. Results suggest that differential outcomes exert their effect independently of differential sample responding. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of fluoxetine given chronically on the responsiveness of 5-HT receptor subpopulations to their agonists

The effect of chronic treatment (5 and 10 mg/kg i.p., twice daily, 14 days) with fluoxetine (FLU), an antidepressant drug which selectively inhibits the reuptake of 5-hydroxytryptamine (5-HT), on the responsiveness of 5-HT receptor subpopulations to their agonists in rats and mice was examined. FLU had no effect on the hypothermia (in mice) and the behavioural syndrome (in rats) induced by 8-OH-DPAT (a 5-HT1A agonist). The m-CPP-induced hypothermia in mice (a 5-HT1B effect) was increased by FLU given chronically. FLU in a single dose decreased that effect. FLU given chronically attenuated the m-CPP-induced hypoactivity in rats (a 5-HT1C effect). The effects mediated by 5-HT2 receptors (L-5-HTP-induced head twitches in mice; fenfluramine-, m-CPP- and TFMPP-induced hyperthermias in rats) were reduced by chronic FLU. The above results indicate that FLU given chronically has no effect on the responsiveness of 5-HT1A receptors, increases the responsiveness of 5-HT1B receptors and decreases those of 5-HT1C and 5-HT2 receptors.     

Effects of human self-assessment responding on learning.

Examined the effects of self-assessment (SA) responding on acquisition rate in paired-associates learning with 190 undergraduates. SA responding required the learner to indicate the degree of sureness in the correctness of each answer by pressing one of several buttons (representing different levels of sureness) either immediately before or after each answer. The number of trials required to learn the names of 8 tools by 20 Ss in each group, who made SA responses using either 2, 4, or 8 SA-response buttons, was compared with the number of trials required by Ss in 3 control groups, who either performed only the learning task or in addition pressed a single button labeled Record either before or after each answer. Results show that acquisition was expedited by as much as 25% by SA responding and was more rapid if the SA response was executed after the answer, rather than before it. The more rapid acquisition is tentatively attributed to a greater ability of the learner who engages in SA responding to identify a correct response. (6 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of varying stimulus size on object recognition in pigeons.

The authors investigated the pigeon's ability to generalize object discrimination performance to smaller and larger versions of trained objects. In Experiment 1, they taught pigeons with line drawings of multipart objects and later tested the birds with both larger and smaller drawings. The pigeons exhibited significant generalization to new sizes, although they did show systematic performance decrements as the new size deviated from the original. In Experiment 2, the authors tested both linear and exponential size changes of computer-rendered basic shapes to determine which size transformation produced equivalent performance for size increases and decreases. Performance was more consistent with logarithmic than with linear scaling of size. This finding was supported in Experiment 3. Overall, the experiments suggest that the pigeon encodes size as a feature of objects and that the representation of size is most likely logarithmic. (PsycINFO Database Record (c) 2010 APA, all rights reserved)