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Toilet training and behaviors of people with autism: parent views.

Individuals with autism often present with toileting problems, yet there is little information about the nature of these problems. This investigation surveyed 100 parents of people with autism of a mean age of 19.5 years. Results indicated that lower cognition and lower verbal levels were significantly correlated with age of accomplishment of bowel and urine training; some subjects were not trained at the time of the study. The average duration of urine training was 1.6 years, bowel training 2.1 years. On the average, training started more than 2 1/2 years before the average age of diagnosis of autism. Fifty-six percent of the sample had to be taught to self-initiate, 42% were taught to ask to use the toilet, and 49% were taught using a schedule. Reinforcement was used by 78% of the parents of males and by 100% of the parents of females. Punishment, primarily scolding was used by 37% of the parents. The most common problems reported were urinating in places other than the toilet, constipation, stuffing up toilets, continually flushing, or smearing feces. More fears related to toileting were noted for verbal subjects.

Activities of Daily Living↗

A searching procedure for transformations and models in a classical Mendelian cross breeding study.

Adopting Wright's four criteria (homogeneity, normality, additivity of effects, and parsimony of parameters needed) concerning a good scale of measurement, a systematic procedure is presented to find an adequate transformation for the data of a classical Mendelian cross. By using Cavalli's least-squares fitting procedure, fits of all possible genetical (sub)models are compared to each other. The model yielding the best fit with as few parameters as possible is selected. More complex models are accepted only if they fit significantly better than simpler ones. Four worked examples are presented from a classical cross study in rats: time till onset of a learned bar-press response under a continuous-reinforcement schedule and protein content, acetylcholinesterase activity, and butyrylcholinesterase activity in the occipital cortex. Using several transformations, invariance of resulting models was found if the criterion of homogeneity of variance was met.

Animals↗

Increasing isolate and social play in severely disturbed children: intervention and postintervention effectiveness.

A group treatment procedure was instituted in Study 1 to increase the isolate and social play of 4 severely disturbed children. The results indicated that play behavior could be increased significantly by the use of food and social reinforcement and by the use of passive shaping, but that it quickly declined when the intervention was terminated. Social play, however, did remain above baseline levels during extinction. Study 2 replicated the results of Study 1 with a second group of older children, also severely disturbed. However, the procedure of fading adult intervention proved an effective method for increasing the resistance of social play to extinction relative to Study 1. A PROCEDURE OF CONtinuous and multiple-observer reliability assessment was employed for both studies, and the positive results and the methodological implications of the procedure are discussed.

Age Factors↗

Increased sensitivity to benzodiazepine antagonists in rats following chronic treatment with a low dose of diazepam.

The effects of benzodiazepine (BZ) antagonists on operant behavior were examined in rats chronically administered a low dose of diazepam (DZ). The low maintenance dose of DZ (5 mg/kg twice daily) was selected as more closely associated with its anxiolytic effects than the higher treatment doses previously used to study BZ dependence. Food-restricted rats were trained to press a lever for food reinforcement under a FR20 schedule of reinforcement prior to the start of DZ administration. Acute administration of DZ caused a dose-dependent reduction of response rates, with 5 mg/kg causing a 50% decrease. Rats treated chronically with DZ became tolerant to its rate-suppressant effects as shown by a 5-fold increase in the dose of DZ required to reduce FR20 response rates by 50%. The BZ antagonist flumazenil (formerly Ro 15-1788; 10-56 mg/kg) suppressed rates of responding in rats treated chronically with DZ. The suppression of operant responding was obtained when flumazenil was given up to 3 h, but not 18 h, after the last treatment with DZ. In contrast, only the highest dose of flumazenil (56 mg/kg) caused reductions of operant responding when given to rats treated with saline. The BZ antagonist CGS 8216 (3.3-33 mg/kg IP), given 10 min prior to the session, was similarly more potent and effective at suppressing operant responding in rats treated chronically with DZ than saline. This procedure may provide a model for the clinical problem of physical dependence to chronically-administered low, anxiolytic doses of BZ tranquilizers.

Animals↗

A comparison of the effects of the novel muscarinic receptor agonists L-689,660 and AF102B in tests of reference and working memory.

Four experiments compared the CNS effects of a novel M1/M3 receptor agonist L-689,660 with those of the M1/M3 muscarinic receptor agonist AF102B. In the mouse tail-flick test of antinociception (TF) the minimum effective doses to increase tail-flick latency (MED) of L-689,660 and AF102B were 0.03 mg/kg and 10.0 mg/kg, respectively. In a rat conditioned-suppression-of-drinking (CSD) test of reference memory, doses of 0.3 and 1.0 mg/kg L-689,660 and a dose of 5.0 mg/kg AF102B reversed a scopolamine-induced deficit in performance (0.6 mg/kg). Although there was a tendency for L-689,660 to reverse the scopolamine-induced (0.4 mg/kg) performance deficit in a rat delayed-matching-to-position (DMTP) test, the difference failed to reach statistical significance. In contrast, a 5.0 mg/kg dose of AF102B potentiated the scopolamine-induced deficit in choice accuracy and the number of trials completed on this task. In a response sensitivity (RS) test, chain-pulling rates were significantly decreased by L-689,660 (MED = 0.03 mg/kg) and by AF102B (MED = 5.0 mg/kg). These results suggest that L-689,660 and AF102B may ameliorate or reverse a scopolamine-induced deficit, but only at doses that also reduce chain-pulling rates on operant schedules of reinforcement.

Animals↗

Comparative effects of preoptic area infusions of opioid peptides, lesions and castration on sexual behaviour in male rats: studies of instrumental behaviour, conditioned place preference and partner preference.

The effects on the sexual behaviour of male rats of excitotoxic amino acid-induced lesions of the medial preoptic area-anterior hypothalamic area (mPOA/AHA), infusions of beta-endorphin, alpha-melanocyte stimulating hormone and naloxone into the mPOA/AHA, systemic naloxone and castration were compared using different behavioural paradigms. These included measures of unconditioned copulatory behaviour, instrumental responses for an oestrous female presented under a second-order schedule of reinforcement, conditioned place preference and partner preference. The results demonstrate that manipulations of the mPOA/AHA markedly affect consummatory aspects of sexual behaviour (mounting, intromitting and ejaculating) but tend not to affect appetitive or reward-related aspects of sexual behaviour, although intra-mPOA/AHA alpha MSH did result in a small increase in instrumental responses, while beta-endorphin infused into the mPOA/AHA also abolished preference for an oestrous over an anoestrous female. Systemic naloxone, on the other hand, reduced instrumental behaviour and a place preference conditioned by prior sexual interaction, while the same compound infused into the mPOA/AHA markedly facilitated copulatory responses but did not affect other measures of appetitive sexual responses. Castration caused an extremely rapid attenuation of conditioned place preference which was apparent before the males had experienced reductions in their copulatory performance. This treatment only slowly reduced partner preference. The results indicate that the use of several behavioural procedures can reveal discrete actions of neuroendocrine treatments on separable psychological processes which underly the integrated pattern of masculine sexual behaviour. In particular, they suggest that the mPOA/AHA is especially concerned with the copulatory responses of mounting and intromitting, but is much less important for a variety of appetitive sexual acts as well as sexual reward, as measured in the place preference procedure. The marked effects of castration on conditioned place preference taken together with the lack of effect of lesions of the mPOA/AHA on this measure indicate that testosterone affects sexual reward-related processes by an action at a site other than the mPOA/AHA. The implications of these findings are discussed.

Animals↗

Naloxone effects on sucrose-motivated behavior.

The opioid system plays an important role in feeding. In general, opioid agonists typically increase feeding and opioid antagonists decrease feeding in non-food restricted animals. In food restricted animals the effects of these drugs are substantially reduced. Opioid antagonists have shown a marked effectiveness at reducing consumption of sweet foods. Explanations for this robust effect have typically focused on drug induced changes in taste, taste perception, or palatability. The current study relates the effects of the opioid antagonist naloxone on motivation to obtain different sucrose concentrations to the drug's effects on unrestricted sucrose solution consumption. Changes in motivation to respond were assessed under a progressive ratio reinforcement schedule (PR) which required increased response cost for each successive unit of sucrose solution. Motivation, as measured by the PR, increased as sucrose concentration increased and naloxone produced a dose-dependent decrease in motivation to respond for a given sucrose concentration. Thus, the effectiveness of naloxone was indirectly related to strength of the sucrose concentration. Under unrestricted access to sucrose solutions, naloxone reduced consumption greatest under the higher concentrations. The data suggest at least part of naloxone's effects on sweet tasting food may be mediated through endogenous opioid reward systems that are reflected in measures of motivation.

Animals↗

Lifelong hyperarousal in the spontaneously hypertensive rat indicated by operant behavior.

Instrumental conditioning techniques were used to obtain objective evidence of differences in behavioral arousal between the spontaneously hypertensive rat (SHR) and the normotensive ancestral Wistar Kyoto (WKY) strain. Subjective emotionality ratings previously indicated that the genetically hypertensive rats were more active and aggressive than their normotensive cousins. In a lengthy series of operant conditioning sessions using a small number of adult female SHR and WKY rats, hyperarousal in the SHR was confirmed by their significantly higher response outputs on either response contingent or time contingent schedules of reinforcement. Conditioned emotionality tests during this series of experiments also suggested hyperarousal and aggressiveness in the SHR, since the fear-conditioned stimulus suppressed bar-pressing in the SHR much less than in the WKY. Further experiments with young prehypertensive SHR rats provided the same evidence of hyperresponsivity in the SHR compared to the WKY strain. Furthermore, these young SHR failed to develop hypertension by the end of the study (14 weeks of age), while their nonconditioned SHR cousins had become clearly hypertensive by the same age. This suggests that factors related to the conditioning methods modified the development of high blood pressure in this animal model of essential hypertension.

Age Factors↗

Potential role for the hypothalamo-pituitary-adrenal axis in the conditioned reinforcer-induced reinstatement of extinguished cocaine seeking in rats.

RATIONALE: We have previously reported that pretreatment with the corticosterone synthesis inhibitor ketoconazole blocks the electric foot-shock-induced reinstatement of cocaine-seeking behavior in rats, suggesting a potential role for the hypothalamo-pituitary-adrenal (HPA) axis in this animal model of relapse. OBJECTIVES: This experiment was designed to investigate whether or not ketoconazole would also inhibit the reinstatement of cocaine seeking induced by the presentation of a conditioned reinforcer. The effects of the corticotropin-releasing hormone 1 (CRH1) receptor antagonist CP-154,526 were also investigated to further determine the involvement of the HPA axis in this behavior. METHODS: Adult male rats were implanted with jugular catheters and trained to self-administer cocaine (0.25 mg/kg per infusion) during daily 2-h sessions. During training, cocaine delivery was paired with the presentation of a tone and the illumination of a house light. Once a stable baseline of cocaine self-administration was observed, lever pressing was extinguished to less than 20% of baseline rates. During reinstatement testing, responding by rats in the contingent group resulted in the presentation of the conditioned reinforcer (i.e., the house light and tone previously paired with self-administered cocaine). Rats in the non-contingent group were presented with the tone/house light compound stimulus once every 5 min, regardless of responding. Rats were pretreated with ketoconazole (25 mg/kg, i.p.) or CP-154,526 (20 mg/kg, i.p.) 30 min prior to testing for reinstatement with the contingent presentation of the conditioned reinforcer to determine the role for the HPA axis in this behavior. RESULTS: The response-contingent presentation of the conditioned reinforcer reliably reinstated extinguished cocaine-seeking behavior, while the non-contingent presentation of the same stimulus did not. Increases in plasma corticosterone were evident during cocaine self-administration as well as during extinction and reinstatement testing. However, while plasma corticosterone returned to basal levels by the end of the session during extinction, it remained elevated through the end of the session during reinstatement. Pretreatment with ketoconazole reversed the conditioned reinforcer-induced reinstatement of extinguished cocaine-seeking behavior and also attenuated the conditioned increases in plasma corticosterone observed during reinstatement. Pretreatment with CP-154,526 resulted in a similar decrease in cocaine seeking. CONCLUSIONS: These data suggest a potential role for the HPA axis in the ability of environmental cues to stimulate cocaine-seeking behavior.

Analysis of Variance↗

Increased vulnerability to self-administer cocaine in mice prenatally exposed to cocaine.

RATIONALE: At least 40,000 infants born each year in the U.S. are estimated to have been exposed to crack cocaine and, therefore, may be at risk for increased vulnerability to cocaine addiction. OBJECTIVES: The present study tested the hypothesis that prenatal exposure to cocaine significantly increased subsequent cocaine-taking behavior in mice. METHODS: Swiss Webster male mice that had been exposed to cocaine in utero were tested at 5 months of age in the cocaine self-administration paradigm. They were the offspring of dams that received one of the following treatments during gestation days 8-17: cocaine (40 mg/kg or 20 mg/kg per day; COC40 and COC20 mice, respectively), saline with access to food ad libitum (SAL mice), or saline with access to food restricted to that of the COC40 dams (i.e., pair-fed; SPF40 mice). Mice were initially trained to lever press for a condensed-milk solution, were implanted with an indwelling intravenous (i.v.) catheter and, subsequently, allowed to self-administer cocaine (0.25, 0.5, 1.0, or 2.0 mg/kg per injection) under a fixed ratio (FR) 1 schedule of reinforcement. RESULTS: Latency for acquisition of food-reinforced responding appeared to be independent of prenatal treatment, as was acquisition of cocaine self-administration, which was found to be dose dependent. Both COC40 and SAL mice reached cocaine self-administration criteria at 1.0 mg/kg or 2.0 mg/kg per injection doses, while neither group did so at lower doses. It was also observed that, at each of the doses tested, a higher number of COC40 mice reached criteria for acquisition. A logistic regression analysis confirmed that the likelihood for acquiring cocaine self-administration was positively correlated to prenatal exposure to cocaine and the dose of cocaine tested. CONCLUSIONS: These data provide evidence, for the first time, that prenatal exposure to higher doses of cocaine increase the probability of acquiring cocaine self-administration at moderate doses during adulthood and modulate vulnerability to cocaine-taking behavior in mice.

Animals↗

Discriminative stimulus properties of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)DOI] in C57BL/6J mice.

RATIONALE: The drug discrimination procedure has proven to be a valuable tool for studying the mechanism of action of psychoactive drugs. Recently, mice with targeted gene mutations have been developed that may also prove useful in evaluating the role of specific receptors in mediating the actions of drugs. We were interested in studying the effects of hallucinogens in genetically modified mice using the drug discrimination procedure. OBJECTIVE: To establish the training procedures and characterize the stimulus properties of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)DOI] versus saline in wild-type mice. METHODS: Using a two-lever drug discrimination procedure, C57BL/6J mice were trained to discriminate (+/-)DOI (2.5 mg/kg) from saline on a VI 30-s schedule of reinforcement. RESULTS: The acquisition function was orderly and similar to that found previously with rats, although the training dose required for the mice was four times higher (2.5 versus 0.75 mg/kg). The dose-response relationship indicated that percent drug lever responding was dose-dependent. Two other hallucinogens, LSD and (-)DOB, substituted fully for (+/-)DOI. Mice were tested for their ability to discriminate (+/-)DOI following pretreatment with the 5-HT(2A) receptor antagonist MDL 100,907, or with 5-HT(2C) selective antagonists, SB 206,553 or SB 242,084. A dose of 0.25 mg/kg MDL 100,907 essentially completely blocked the discriminative stimulus effects of 2.5 mg/kg (+/-)DOI. Surprisingly, both SB 206,553 and SB 242,084 also attenuated the effect of 2.5 mg/kg (+/-)DOI. The effect of SB 206,553 was surmountable at 5.0 mg/kg (+/-)DOI. CONCLUSIONS: These data agree with the results from studies with rats indicating a prominent role for the 5-HT(2A) receptors in mediating the discriminative stimulus effects of (+/-)DOI but in addition, suggest a small but significant role for the 5-HT(2C) receptor in mice.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗