Transplacental cocaine exposure. 1: A rodent model

Contaminated groundwater poses a significant health hazard and may also impact wildlife such as amphibians when it surfaces. Using FETAX (Frog Embryo Teratogenesis Assay-Xenopus), the developmental toxicity of ground and surface water samples near a closed municipal landfill at Norman, OK, were evaluated. The groundwater samples were taken from a network of wells in a shallow, unconfined aquifer downgradient from the landfill. Surface water samples were obtained from a pond and small stream adjacent to the landfill. Surface water samples from a reference site in similar habitat were also analyzed. Groundwater samples were highly toxic in the area near the landfill, indicating a plume of toxicants. Surface water samples from the landfill site demonstrated elevated developmental toxicity. This toxicity was temporally variable and was significantly correlated with weather conditions during the 3 days prior to sampling. Mortality was negatively correlated with cumulative rain and relative humidity. Mortality was positively correlated with solar radiation and net radiation. No significant correlations were observed between mortality and weather parameters for days 4-7 preceding sampling.     

Interactive effects of cocaine and gender on thymocytes: a study of in vivo repeated cocaine exposure

This study used a mouse model including both sexes to assess the impact of repeat cocaine exposure on the differentiation and function of T cell in thymus. Cocaine hydrochloride in 0.9% saline, 5 mg or 40 mg/kg, was administrated by i.p. injection to C57BL/6 mice for 10 days. Thymocytes were obtained 24 h after the 10th injection. Repeat in vivo cocaine exposure inhibited the proliferation of T lymphocytes in response to Con-A and Con-A plus anti-CD28. The proliferation induced by IL-2 in the Con-A stimulated T blasts was attenuated in cocaine treated mice. These effects were seen at a lower cocaine dose in female mice. The total number of thymocytes was reduced. Although the percentage of mature thymocytes (CD4+ CD8- and CD4- CD8+ cells) was not altered, the absolute cell numbers were attenuated. Both percentage and absolute cell number of immature thymocytes (CD4+ CD8+) decreased and the pre-mature (CD4- CD8-) cells increased. CD28 and CD25 expression were attenuated in Con-A stimulated thymocytes of mice treated with cocaine at 40 mg/kg. Interleukin 2 production was not significantly altered, however, gamma-IFN production was decreased by cocaine exposure at 40 mg/kg. In conclusion, cocaine exerts inhibitory effects on the function of mature thymocytes, and on the differentiation of thymocytes. A gender difference in response to cocaine was noted in that female mice were more sensitive to lower dose of cocaine exposure.     

Neonatal exposure to bFGF exerts NGF-like effects on mouse behavioral development

Metabolic products secreted by the fungal mycelia of Hirsutella thompsonii var. thompsonii (CBS 556.77D) in a defined culture broth in shake culture were tested for toxicity to Galleria mellonella larvae and Drosophila melanogaster adults via injection and per os application, respectively. In addition, the toxic effect of broth filtrate was observed in vitro in a cell line of Bombyx mori. Czapek-Dox broth fortified with 1% yeast extract stimulated more rapid mycelial growth and correspondingly more toxin production in time. At 25-30 degrees C, metabolic toxin(s) was detected in broth via bioassay at about 4-5 days postinoculation when mycelial biomass reached 5 mg/ml (dry wt). At these temperatures, biological activity of the filtrate peaked at about 8-10 days when mycelial growth reached a maximum (10 mg/ml, dry wt). This suggests a positive relationship between toxic metabolite and mycelial production. After 10 days, the toxicity of the filtrate appeared to decline gradually. Pathogenicity symptoms of the metabolites developed slowly in both G. mellonella and D. melanogaster. Early signs of lethargy appeared at 4 days postinjection and cumulative mortality of G. mellonella larvae was low after 1 week; however, the percentage of mortality reached 98-100% after 14 days. At death, G. mellonella larvae displayed small dark spots on a brownish cuticle. Histopathological effects were observed in the larval midgut, malpighian tubules, hypodermis, fat body, hemocytes, muscle, and silk glands. Cellular change consisted of pycnosis of the nucleus and a reduction in cytoplasm density. Highest mortality (78.8%) to adult D. melanogaster occurred after 10 days post-treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stable chronic disease: a behavioral model

A three-year study was undertaken in the general medical clinic of a private community hospital, to assess the health behavior, health status, and profile of function of stable chronic disease was developed and tested. It was shown that these patients used a disproportionate amount of health care services. Half of the group was treated by a nurse practitioner/physician team and half by a house officer/preceptor team. Patients in both groups behaved similarly. These patients: 1) made frequent demands for outpatient services but did not need more than average hospital care; 2) tended to have problems of socio-economic indigency; 3) were likely to have hypertension, obesity, arthritis, and functional disease; 4) were chiefly women; 5) required special visits 9 percent of the time, usually for exacerbations of illness or intercurrent health problems; 6) made greater demands if they had functional complaints as a primary or secondary health problem; and 7) viewed their health more positively and functioned at a higher level if they were over 65 years of age. It was also found that the nurse practitioner, working in consultation with a physician, was able to provide high-quality health care.     

Outpatient behavioral treatment for cocaine dependence: One-year outcome.

This article describes outcomes observed during the year after treatment entry from two controlled trials in which cocaine-dependent outpatients were randomly assigned to either a multicomponent behavioral treatment or to one of two control treatments. The behavioral treatment integrated the community reinforcement approach (CRA) with an incentive program in which cocaine abstinence was reinforced with vouchers exchangeable for retail items. The two control treatments were drug abuse counseling and CRA without the incentive program. All treatment groups improved significantly compared to intake, and those changes were maintained through the follow-up period. When efficacy differences were observed during treatment and follow-up, they supported CRA with vouchers over control treatments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Different effects of methylxanthines on central serotonergic postsynaptic neurons in a mouse behavioral model

We have used genetic engineering to obtain secretion of anti-human CD5 antibody fragments from Escherichia coli for conjugation to the 30-kDa form of ricin A chain (RTA30). This was accomplished by introducing stop codons at two positions in the hinge region of the human IgG1 gene so that coexpression of the truncated heavy-chain genes (Fd') with a light chain would result in Fab' and/or F(ab')2 proteins containing either one or two interheavy-chain cysteines. An Fd' gene encoding both interheavy-chain cysteines yielded a mixture of F(ab')2 and Fab', which could be separated by size-exclusion chromatography. An Fd' gene encoding only one interheavy-chain cysteine yielded primarily Fab'. Purified F(ab')2 protein was equivalent to unlabeled chimeric IgG in competing for binding of IgG with CD5 antigen, while the molar concentration of the monovalent Fab' required for 50% binding inhibition was 4- to 5-fold higher than IgG. An immunoconjugate was prepared with Fab' by direct coupling to the unique free cysteine on RTA30. The bivalent F(ab')2 was conjugated to RTA30 after derivatization with the crosslinking agent 5-methyl-2-iminothiolane. These immunoconjugates efficiently killed a CD5+ T-cell line and human peripheral blood T cells.     

In utero cocaine exposure and language development

A growing body of literature suggests that in utero cocaine exposure may place a child at risk for impaired language development. Because the field of gestational drug exposure and its effects on communicative development is young, the research is still limited and the data are contradictory, plagued by many methodological problems. The accumulating evidence, however, suggests that the development of specific aspects of language may be compromised in a percentage of children and that outcome is affected by a wide range of prenatal and postnatal biological and environmental factors. The data also suggest that deficits are best identified through the use of focused test batteries and may be evident only under stressful or difficult conditions. This article provides a critique and general overview of the literature on the early communicative and language development of prenatally cocaine-exposed children. Potential reasons for compromised language development and the clinical implications of these findings are discussed.     

The role of catecholamines in cocaine toxicity: a model for cocaine "sudden death"

Sudden death associated with cocaine abuse is preceded by a state of agitated delirium. We postulated that release of catecholamines associated with this stress enhanced toxicity from cocaine. Thus we investigated the effect of catecholamine infusion [(epinephrine (7.25 ugml-1), norepinephrine (4.4 ugml-1) and dopamine (8.0 ugml-1), infused at 6 ml h-1] on the toxicity from concomitant infusion of cocaine (1 mg-kg-1 min-1). Two groups of rats were studied in order to isolate distinct toxicity endpoints: convulsions and respiratory arrest in conscious, and, circulatory arrest in anesthetized and ventilated rats. Catecholamines were administered at either full or 1/2 strength to establish a dose response effect on cocaine toxicity. Catecholamine infusion in a dose dependent fashion provoked earlier convulsions and respiratory arrest in conscious rats and circulatory arrest in anesthetized and ventilated rats. Despite lower cocaine cumulative dose administration, rats receiving catecholamines had similar plasma cocaine concentrations at the onset of convulsions and respiratory arrest compared to those with cocaine infusion alone. The data suggest that catecholamines enhance the convulsive, respiratory and circulatory toxicity of cocaine by a pharmacokinetic interaction.     

A laboratory model of cocaine withdrawal in humans: Intravenous cocaine.

Seven adult intravenous (IV) cocaine users completed a protocol investigating changes in behavior after the self-administration of cocaine. During sessions, the participants could self-administer up to 6 doses of IV cocaine (32 mg/70 kg) twice each day. Both 2- and 3-day binge conditions were tested. At 39 hr after the 3-day but not the 2-day binge of cocaine use, total Beck Depression Inventory scores were increased and participants reported increased ratings of Irritable and decreased ratings of I Want Cocaine. Exposure to stimulus cues associated with IV cocaine increased ratings of I Want Cocaine during periods of abstinence after both 2- and 3-day binges and increased ratings of Depressed only after the 3-day binge of cocaine use. The cessation of binge cocaine use produced modest changes in mood and cocaine craving that were related to the length of the binge and varied as a function of time since last cocaine use. Responsiveness to cocaine cues also varied as a function of the length of the previous cocaine binge. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Training behavioral school psychologists: Development of a model.

Suggests that the lack of consensus within the field of school psychology concerning appropriate functions and roles for school psychologists presents a dilemma to trainers attempting to match curricula to a model of professional practice or service delivery. It is also suggested that a behavioral school psychology model can be integrated across various conceptual levels, provides a coherent philosophy of service delivery, and derives a set of practices from a strong research base. A training model based on behavioral school psychology is described, and examples from a training program are offered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Promoting smoking cessation among cancer patients: a behavioral model

The smoking cessation clinical practice guideline recently published by the Agency for Health Care Policy and Research (AHCPR) summarizes current knowledge on smoking cessation treatments. Among its recommendations, the guideline encourages physicians to motivate patients who indicate that they are not yet ready to quit smoking. Because medical training typically emphasizes pharmacologic rather than behavioral treatment, we believe that physicians caring for cancer patients may benefit from more extensive instruction in motivating patients to quit smoking. This article describes how a contemporary theoretical approach, the transtheoretical model of change, can be used to promote behavioral change. Multiple studies, primarily in the field of smoking cessation, provide strong empiric support for use of this model in clinical practice. The model consists of five stages of smoking cessation that describe different levels of readiness to quit: precontemplation, contemplation, preparation, action, and maintenance. A diagnostic tool is presented, and specific smoking cessation counseling strategies are suggested for each stage of change. Implications for the use of the model by physicians who counsel and treat smokers are discussed.     

Neurochemical and behavioral evidence supporting (+)-AJ 76 as a potential pharmacotherapy for cocaine abuse

In vivo microvoltammetry was used to detect synaptic concentrations of dopamine (DA) and serotonin (5-HT) from nucleus accumbens (NAcc) in awake, freely moving, male, Sprague Dawley laboratory rats, while their locomotor behavior was monitored, simultaneously, in an open-field paradigm; the purpose was to evaluate the pharmacology of the D3-preferring, dopamine (DA) autoreceptor antagonist, (+)-AJ 76 [cis-(+)-1S, 2R-5-methoxy-1-methyl-2-(n-propylamino)-tetralin HCL] and its potential use as a pharmacotherapy for cocaine abuse. Results showed that (1). (+)-AJ 76 significantly increased synaptic concentration of DA above baseline (p < 0.001); a small but significant decrease in synaptic concentration of 5-HT was seen (p < 0.001), although a significant increase occurred during the time course, at the 20 minute mark (p < 0.05). Analysis of the two hour data also showed that both locomotor and central locomotor activity were not affected; however, temporally related increases in both behaviors were significant at 10, 20 and 30 minutes (p < 0.05). In a second and separate study, (2). cocaine increased synaptic concentrations of DA (p < 0.001) and 5-HT (p < 0.001), and locomotor activity (p < 0.001) above baseline, but central locomotion was not affected, except for specific temporal enhancements at 10, 20, 30, 50, 60 and 90 min. (p < 0.05). In a third and separate study, (3). an (+)-AJ 76/cocaine study, (+)-AJ 76 was administered five minutes before cocaine. The results showed that synaptic DA concentration was significantly increased over baseline values (p < 0.001) but that synaptic DA was lower than cocaine-induced synaptic DA (p < 0.001). No significant difference in synaptic 5-HT occurred after (+)-AJ 76/cocaine treatment, but temporally related increases over baseline occurred from 10 to 40 min. (p < 0.05). Synaptic 5-HT concentrations after (+)-AJ 76/cocaine were not significantly different from those induced by cocaine per se. (+)-AJ 76/cocaine treatment significantly increased locomotor activity (p < 0.001); central locomotor behavior was not affected, however, time course data showed significant increases at 10, 20, 40, 50 and 80 min. (p < 0.05). The major finding from the present studies, is that +(-) AJ 76/cocaine treatment produced synaptic concentrations of DA from NAcc which were lower than those due to cocaine per se, while no differential effect on synaptic 5-HT concentration, locomotor or central locomotor behavior occurred. Therefore, these data support the hypothesis that (+)-AJ 76 may be useful for the treatment of cocaine addiction or abuse.     

Prenatal exposure to cocaine: effects on aggression in Sprague-Dawley rats

Social/aggressive behavior in adult rat offspring (beginning at postnatal Day 180) prenatally exposed to saline, cocaine, or amfonelic acid (AFA) was examined. Pregnant rats received injections of 15 mg/kg of cocaine, or 0.9% saline twice daily, s.c., or on 2 consecutive days at 4-day intervals, or 1.5 mg/kg amfonelic acid daily throughout gestational Days 1-20. Frequency, duration, and latency of 11 social/aggressive behaviors were recorded for two 15-min sessions during which a smaller male intruder replaced an ovariectomized female in the resident's home cage. Subjects received a s.c. saline injection before Session 1 and 2.0 mg/kg of gepirone, a 5HT1a partial agonist, prior to Session 2. Prenatal cocaine treatment resulted in alterations of aggressive behavior. Aggressive behavior was reduced by gepirone in all groups but to a lesser extent in the AFA group.     

Transplacental and immediate effect of ortho-aminoazotoluol on organ cultures of embryonal mouse liver

A study was made of the transplacental and direct action of orthoaminoazotoluol (OAAT) in the organ cultures of the embryonic liver of mice of a highly hepatomic CBA line. In direct action in vitro OAAT caused a marked reduction of survival of the organ cultures of the embryonic liver in comparison with control. In the transplacental action of OAAT the toxic effect was replaced at the last periods of cultivation by the growth stimulating one; the percentage of live experimental cultures increased by 30 in comparison with control.     

Contingency management and levodopa-carbidopa for cocaine treatment: A comparison of three behavioral targets.

New data support use of levodopa pharmacotherapy with behavioral contingency management (CM) as one efficacious combination in cocaine dependence disorder treatment. A potential mechanism of the combined treatment effects may be related to dopamine-induced enhancement of the saliency of contingently delivered reinforcers. Evidence to support this mechanism was sought by evaluating levodopa-enhancing effects across distinct CM conditions that varied in behavioral targets. A total of 136 treatment-seeking, cocaine dependent subjects participated in this 12-week, randomized, placebo-controlled trial of levodopa (vs. placebo) administered in combination with one of three behavioral CM conditions. In the CM-URINE condition, subjects received cash-valued vouchers contingent on cocaine-negative urine toxicology results. In the CM-ATTEND condition, the same voucher schedule was contingent on attending thrice weekly clinic visits. In the CM-MEDICATION condition, the same voucher schedule was contingent on Medication Event Monitoring Systems- and riboflavin-based evidence of pill-taking behavior. Primary outcomes associated with each CM target behavior were analyzed using generalized linear mixed models for repeated outcomes. CM responding in the CM-ATTEND and CM-MEDICATION conditions showed orderly effects, with each condition producing corresponding changes in targeted behaviors, regardless of medication condition. In contrast, CM responding in the CM-URINE condition was moderated by medication, with levodopa-treated subjects more likely to submit cocaine-negative urines. These findings specify the optimal target behavior for CM when used in combination with levodopa pharmacotherapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A case history demonstrating the complementary use of psychodynamic and behavioral techniques in psychotherapy.

Presents a case history that demonstrates a successful combination of psychodynamic and behavioral techniques in the treatment of a married graduate student in his mid-30's who presented with a dysfunctional anxiety about studying, fear of criticism, and feeling uncomfortable in groups. S was first treated behaviorally, using systematic desensitization, to decrease study anxiety and then psychodynamically to assist in the understanding and working through of underlying fears of failure. Theoretical formulations and objections related to the approach are discussed. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Taste of sugars: Brief exposure single-stimulus behavioral method.

Used a brief exposure, single-stimulus test procedure to assess taste of sugars in 86 male Fischer rats. Ss were trained to sample the test solution immediately upon presentation. Intake was measured periodically for 10 min using fructose, glucose, or sucrose as a stimulus and water as a control. The stimulus-response functions and kinetics were different for the 3 sugars. Relative "sweetness" was predicted from the data to be sucrose > fructose > glucose. This prediction was confirmed by additional brief-exposure tests as well as by a 3-choice 24-hr test. Control experiments using a 2-choice 24-hr preference test showed that glucose was ingested preferentially. The brief exposure single-stimulus method appears to give a clearer indication of taste effectiveness than does the classical 2-choice 24-hr preference test. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tolerance and sensitization to the behavioral effects of cocaine in rats: relationship to benzodiazepine receptors

Tolerance and sensitization to the behavioral effects of cocaine were investigated in rats responding under a fixed-consecutive-number eight schedule of food reinforcement. The development of tolerance or sensitization was induced by delivering the drug either immediately before or after each behavioral session during chronic administration. Chronic cocaine administered before each session resulted in tolerance, as indicated by the shift to the right in the cocaine dose response curve. This tolerance was more likely to develop in the presence of an external discriminative stimulus. On the other hand, when cocaine was delivered after each session, the injections did not disrupt responding and sensitization or increased sensitivity rather than tolerance developed. This sensitization was more likely to occur when the external discriminative stimulus was not present. These data suggest that either tolerance or sensitization to the behavioral effects of cocaine can occur following the same number of chronic injections, with the effect dependent on the context under which the drug is delivered. Significant differences in benzodiazepine receptor binding measured autoradiographically using [3H]flumazenil were observed between rats that received cocaine before or after each session, suggesting that the development of tolerance and sensitization may be mediated through changes in benzodiazepine receptors in discrete brain regions.