Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats. (1/30)

Melatonin (MEL) is a widely used, over-the-counter sleep aid, and it has putative contraceptive, antioxidant, antiaging, and anticancer effects. The developmental toxicity potential for repeated oral doses of MEL had not previously been evaluated. In the present studies, time-mated, Sprague-Dawley-derived (CD) rats were administered MEL or vehicle by gavage on gestation days (gd) 6-19. MEL-treated groups received 1-, 10-, 100-, 150-, or 200-mg/kg body weight/day in the screening study (15 rats/group), and 50, 100, or 200 mg/kg/day in the definitive study (25 rats/group). In both studies, maternal food/water consumption, body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20, both studies), maternal liver and gravid uterine weights, number of ovarian corpora lutea, conceptus survival, fetal sex, and fetal body weight were evaluated. Fetal morphological examination included external structures (both studies) as well as visceral and skeletal structures (definitive study). In the screening study, maternal serum levels of 17beta-estradiol, progesterone, prolactin, and luteinizing hormone were determined by radioimmunoassay, and mammary tissue was fixed, stained, and evaluated for percent glandular area within the fat pad. No maternal morbidity/mortality was found in either study. In the screening study, aversion to treatment (> or =100 mg/kg/day) and reduced maternal weight gain (> or =150 mg/kg/day) were noted, but reproductive/endocrine parameters and fetal development were not affected. In the definitive study, aversion to treatment was noted at > or =50 mg/kg/day, and mild sedation, reduced maternal food intake, and reduced body weight gain were found during initial treatment with 200 mg/kg/day. MEL had no effect on prenatal survival, fetal body weight, or incidences of fetal malformations/variations. Thus, in the definitive study, the maternal toxicity NOAEL and LOAEL were 100 and 200 mg/kg/day, respectively, and the developmental toxicity NOAEL was > or =200 mg/kg/day.  (+info)

Paradigm to test a drug-induced aversion to ethanol. (2/30)

The screening of new agents for aversive therapy of alcoholism requires a simple animal model. Animals trained to ingest ethanol solutions and subsequently administered a drug known to produce an aversion to ethanol in humans, do not readily make the association between the malaise induced by the aversive drug-ethanol reaction and the consumption of the same ethanol-containing solution that has been consumed previously without ill effects. An experimental paradigm is reported in which the malaise of the drug-ethanol reaction is quickly recognized by rats as derived from ethanol. Disulfiram was used as the model drug. Lewis rats were deprived of water for 18 h after which 6% (v/v) ethanol was offered as the only fluid. During the first hour of ethanol access, both controls (vehicle) and disulfiram (100 mg/kg)-treated animals consumed intoxicating amounts of ethanol (0.7-0.9 g ethanol/kg). Plasma acetaldehyde levels developed were 3-5 microM and 40-50 microM in the two groups respectively. After this time, disulfiram-treated animals virtually ceased consuming alcohol (90% inhibition), indicating that the disulfiram-ethanol reaction is associated with alcohol ingestion. Control animals continued consuming the alcohol solution for the additional 4-5 h tested. This model should be of value in the testing of new agents that reduce aldehyde dehydrogenase levels for prolonged periods for their potential as an aversive treatment in alcoholism.  (+info)

The aversive control of excessive alcohol consumption by chronic alcoholics in the laboratory setting. (3/30)

The efficacy of several methods of aversive control of excessive alcoholic drinking was investigated in a semi-naturalistic setting that permitted objective measurement of the drinking behavior of chronic alcoholics. Studies 1A and 1B compared an excape-conditioning precedure with a control procedure in which aversive electrical shocks were administered before drinking. Neither procedure effectively decreased subjects' pretreatment, baseline alcoholic drinking behavior. In Study 2, aversive response-contingent shocks effectively suppressed alcoholic drinking, but drinking subsequently returned to its former levels after withdrawal of punishment. Self-administered shock appeared to be as effective as experimenter-administered punishment for controlling drinking, even when the punishment contingency was faded out over time. Study 3 replicated the suppressant effect of punishment, and demonstrated that contingent shock was significantly more effective than yoked, noncontingent shock. A direct comparison of self-versus experimenter-administered punishment suggested a possible slight advantage for the latter.  (+info)

Punishment of self-injurious behavior using aromatic ammonia as the aversive stimulus. (4/30)

Punishment with aromatic ammonia was used to eliminate self-injurious behavior of an autistic woman during experimental sessions. The effects were reversible but were limited to experimental sessions until staff used the ammonia on the ward at all times.  (+info)

Conditioning taste aversions to locoweed (Oxytropis sericea) in horses. (5/30)

Locoweed (Oxytropis sericea) is a serious poisoning problem for horses grazing on infested rangelands in the western United States. Our objectives were to determine 1) whether lithium chloride or apomorphine would condition aversions to palatable foods, and at what doses, and 2) whether horses could be averted to fresh locoweed in a pen and grazing situation. Apomorphine was not an acceptable aversive agent because at the dose required to condition an aversion (> or = 0.17 mg/kg BW), apomorphine induced unacceptable behavioral effects. Lithium chloride given via stomach tube at 190 mg/kg BW conditioned strong and persistent aversions to palatable feeds with minor signs of distress. Pen and grazing tests were conducted in Colorado to determine if horses could be averted to fresh locoweed. Pen tests indicated that most horses (5/6) were completely averted from locoweed. Treated horses ate 34 g of fresh locoweed compared to 135 g for controls (P < 0.01) during three pen tests when offered 150 g per test. One horse (T) in the treatment group ate locoweed each time it was offered in the pen, but ate no locoweed while grazing. In the grazing trial, control horses averaged 8.6% of bites of locoweed (P < 0.01) during the grazing portion of the study, whereas treated horses averaged <0.5%. One treated horse (S) accounted for all consumption; he consumed 15% of his bites as locoweed in a grazing bout on d 2 of the field study. Thereafter, he was dosed a second time with lithium chloride and ate no locoweed in the subsequent 5 d. Three of six horses required two pairings of lithium chloride with fresh locoweed to condition a complete aversion. The results of this study indicate that horses can be averted from locoweed using lithium chloride as an aversive agent, and this may provide a management tool to reduce the risk of intoxication for horses grazing locoweed-infested rangeland.  (+info)

Comparison of larkspur alkaloid extract and lithium chloride in maintaining cattle aversion to larkspur in the field. (6/30)

Lithium chloride (LiCl) and larkspur (Delphinium barbeyi) alkaloid extract were compared in their effect as an emetic to create taste aversions to fresh larkspur. They were further compared in the field to determine whether the indigenous larkspur alkaloids were more effective in maintaining the aversion when conditioned cattle were subjected to the social pressure (social facilitation) of control cattle eating larkspur. Taste aversions were produced in two groups of 1-yr-old cattle by offering fresh larkspur and then gavaging with either LiCl at 200 mg/kg of BW or larkspur alkaloid extract at 1.1 to 1.6 mL/kg of BW. The third group (control) was gavaged with water. The alkaloid group was slower to form an aversion than the lithium group, requiring four doses compared with two doses. All groups were then taken to larkspur-infested rangeland to test the aversion in the field. In the first field trial in which groups grazed separately, both aversion-induced groups generally abstained from eating larkspur. In the second trial in which all groups grazed together, both aversion-induced groups consumed less than half as much larkspur as the controls, but neither group abstained completely. Larkspur alkaloids did not maintain the aversion to larkspur to a greater degree than did LiCl when aversion-induced cattle were subjected to social facilitation.  (+info)

Gentle teaching and applied behavior analysis: a critical review. (7/30)

In recent years, there has been a growing controversy surrounding gentle teaching. This paper explores the nature of this controversy with particular reference to the relationship between gentle teaching and applied behavior analysis. Advantages and disadvantages of this approach are discussed, and it is suggested that gentle teaching and applied behavior analysis need not be regarded as mutually exclusive approaches to working with persons with mental retardation.  (+info)

Narrative Exposure Therapy as a treatment for child war survivors with posttraumatic stress disorder: two case reports and a pilot study in an African refugee settlement. (8/30)

BACKGROUND: Little data exists on the effectiveness of psychological interventions for children with posttraumatic stress disorder (PTSD) that has resulted from exposure to war or conflict-related violence, especially in non-industrialized countries. We created and evaluated the efficacy of KIDNET, a child-friendly version of Narrative Exposure Therapy (NET), as a short-term treatment for children. METHODS: Six Somali children suffering from PTSD aged 12-17 years resident in a refugee settlement in Uganda were treated with four to six individual sessions of KIDNET by expert clinicians. Symptoms of PTSD and depression were assessed pre-treatment, post-treatment and at nine months follow-up using the CIDI Sections K and E. RESULTS: Important symptom reduction was evident immediately after treatment and treatment outcomes were sustained at the 9-month follow-up. All patients completed therapy, reported functioning gains and could be helped to reconstruct their traumatic experiences into a narrative with the use of illustrative material. CONCLUSIONS: NET may be safe and effective to treat children with war related PTSD in the setting of refugee settlements in developing countries.  (+info)

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