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The objective of this study is to describe the longitudinal patterns of depression, anxiety, and stress symptoms from pregnancy to 5 years postpartum, in a cohort of Australian mothers experiencing adversity. Longitudinal data were drawn from the control group of a trial of nurse home visiting. Pregnant women experiencing adversity (≥ 2 of 10 adversity risk factors) were recruited from antenatal clinics across 2 Australian states (30 April 2013–29 August 2014). Women completed the Depression Anxiety and Stress Scales short-form (DASS-21) at 11 time-points from pregnancy to 5 years postpartum. DASS-21 scores were summarized at each time-point for all women and by level of adversity risk. Three hundred fifty-nine women (100%) completed the DASS-21 in pregnancy and 343 (96%) provided subsequent data. Mental health symptoms were highest in pregnancy and at 4 and 5 years postpartum. While this pattern was comparable across levels of antenatal adversity risk, women with greatest adversity risk had consistently higher mental health symptoms. In a cohort of mothers experiencing adversity, depression, anxiety, and stress symptoms were highest in pregnancy and at 4 to 5 years postpartum. The striking patterns of persistent, high, mental health symptoms, beyond the first year postpartum, can inform a more equitable and responsive health system. [ABSTRACT FROM AUTHOR]

Background: The Paediatric Quality of Life InventoryTM 4.0 Generic Core Scales (PedsQL) is a non-preference based instrument for assessing health related quality of life (HRQoL) in children. Recent papers presented algorithms of parental proxy and short-form versions of the PedsQL onto the validated preference-based Child Health Utility 9D (CHU9D) instrument, to enable conversion of PedsQL scores to quality adjusted life years for use in economic evaluation. However, further research was needed to both validate these algorithms, and assess if use of the full 23-item PedsQL self-report instrument is preferable to other PedsQL versions for mapping onto child self-report CHU9D utilities.Objective: To develop a mapping algorithm for converting the 23-item PedsQL instrument onto the CHU9D instrument and provide an external validation of two recently published algorithms that might be considered alternatives.Methods: Data from children in the Longitudinal Study of Australian Children (LSAC) were used (N = 1801). Six econometric methods were compared to identify the best algorithms, assessed against a series of goodness-of-fit criteria. The same data and goodness-of-fit criteria were used in the external validation exercise for previously published mapping algorithms.Results: The optimal mapping algorithm was identified, which used PedsQL dimension scores to predict the CHU9D utilities. It performed well against standard goodness-of-fit tests. The external validation exercise revealed the recently published alternative algorithms also performed relatively well.Conclusion: The identified mapping algorithms can be used to facilitate cost-utility analysis in comparable populations when only the PedsQL instrument is available. Results from this population indicate the algorithms identified in this paper are well suited for estimating CHU9D self-report utilities when the full 23-item self-report PedsQL instrument has been used. [ABSTRACT FROM AUTHOR]

This mixed methods study examines the benefits of basing a family support worker (FSW) at a primary school in Melbourne, Australia. The school has a number of high needs families requiring extensive support from school staff. Pre and post intervention data was collected on the time spent on social problems in the school community. These included managing students with behavioural and emotional issues, providing support and practical assistance to parents with problems and liaising with agencies to access support for students and families. Pre and post intervention Strengths and Difficulties Questionnaires were completed by teachers whose students and families were clients of the FSW (n = 8) and compared with non clients (n = 10). Semi-structured interviews were held with FSW clients (n = 6), class teachers (n = 3) the assistant principal, principal and the FSW. Employing a FSW showed a reduction in the amount of time spent on welfare cases for teachers, and therefore a monetary saving for the school. Qualitative data collected from school staff and FSW clients was overwhelmingly positive. Having a FSW based at a primary school provides savings in teacher time, and expenses to the school. Teachers are freed to concentrate on education and the parents valued the relationship provided by the FSW. [ABSTRACT FROM AUTHOR]

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Asenapine, a novel psychopharmacologic agent in the development for schizophrenia and bipolar disorder, has high affinity for serotonergic, α-adrenergic, and dopaminergic receptors, suggesting potential for antipsychotic and cognitive-enhancing properties. The effects of asenapine in rat models of antipsychotic efficacy and cognition were examined and compared with those of olanzapine and risperidone. Amphetamine-stimulated locomotor activity (Amp-LMA; 1.0 or 3.0 mg/kg s.c.) and apomorphine-disrupted prepulse inhibition (Apo-PPI; 0.5 mg/kg s.c.) were used as tests for antipsychotic activity. Delayed non-match to place (DNMTP) and five-choice serial reaction (5-CSR) tasks were used to assess short-term spatial memory and attention, respectively. Asenapine doses varied across tasks: Amp-LMA (0.01–0.3 mg/kg s.c.), Apo-PPI (0.001–0.3 mg/kg s.c.), DNMTP (0.01–0.1 mg/kg s.c.), and 5-CSR (0.003–0.3 mg/kg s.c.). Asenapine was highly potent (active at 0.03 mg/kg) in the Amp-LMA and Apo-PPI assays. DNMTP or 5-CSR performance was not improved by asenapine, olanzapine, or risperidone. All agents ( P < 0.01) reduced DNMTP accuracy at short delays; post hoc analyses revealed that only 0.1 mg/kg asenapine and 0.3 mg/kg risperidone differed from vehicle. All active agents (asenapine, 0.3 mg/kg; olanzapine, 0.03–0.3 mg/kg; and risperidone, 0.01–0.1 mg/kg) significantly impaired 5-CSR accuracy ( P < 0.05). Asenapine has potent antidopaminergic properties that are predictive of antipsychotic efficacy. Asenapine, like risperidone and olanzapine, did not improve cognition in normal rats. Rather, at doses greater than those required for antipsychotic activity, asenapine impaired cognitive performance due to disturbance of motor function, an effect also observed with olanzapine and risperidone. [ABSTRACT FROM AUTHOR]

Recreational users of (±)3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) exhibit poor performance on a number of neurocognitive measures, with tests of memory and attention most commonly affected. Cognitive impairments can be persistent or possibly permanent, since users who have been abstinent from MDMA for many months are also impaired. Repeated treatment of rats or nonhuman primates with MDMA has consistently been demonstrated to produce specific, lasting depletions of brain serotonin (5-HT) markers, a potential source of such cognitive symptoms. We have shown, however, that monkeys treated with a regimen of MDMA (4 days, 10 mg/kg i.m., b.i.d.), sufficient to produce a 50% reduction of the 5-HT metabolite 5-hydroxyindoleacetic acid in cerebrospinal fluid, do not exhibit lasting deficits in a range of cognitive domains. Acute drug challenges are often effective at unmasking consequences of amphetamine toxicity. Here, the performance of MDMA-treated and control monkeys on tests of spatial working memory (self-ordered spatial search), vigilance and reaction time (5-choice reaction time), reinforcer efficacy and sustained attention (progressive ratio responding) and fine motor control (bimanual motor skill task) was challenged with ketanserin (0.1–1.7 mg/kg, i.m.), 1-(3-Chlorophenyl)piperazine dihydrochloride (mCPP, 0.03–0.5 mg/kg, i.m.) and (±)8-hydroxy-DPAT hydrobromide (8-OH-DPAT, 0.032–0.1 mg/kg, i.m.). MDMA-exposed animals exhibited increased sensitivity to challenge with mCPP on the reaction time and progressive ratio tasks but otherwise were equivalently sensitive to drug challenge. Post-mortem analysis demonstrated that 76–93% reductions of 5-HT in neocortex persist 17–20 months post-MDMA. These observations suggest that large depletions of brain 5-HT produced by MDMA can persistently alter behavioral sensitivity to the disrupting effects of serotonergic agents. [Copyright &y& Elsevier]

Corticotropin-releasing hormone (Crh) is a critical coordinator of the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, Crh released from the paraventricular nucleus (PVN) of the hypothalamus activates Crh receptors on anterior pituitary corticotropes, resulting in release of adrenocorticotropic hormone (Acth) into the bloodstream. Acth in turn activates Acth receptors in the adrenal cortex to increase synthesis and release of glucocorticoids. The receptors for Crh, Crhr1 and Crhr2, are found throughout the central nervous system and periphery. Crh has a higher affinity for Crhr1 than for Crhr2, and urocortin (Ucn), a Crh-related peptide, is thought to be the endogenous ligand for Crhr2 because it binds with almost 40-fold higher affinity than does Crh (ref. 2). Crhr1 and Crhr2 share approximately 71% amino acid sequence similarity and are distinct in their localization within the brain and peripheral tissues. We generated mice deficient for Crhr2 to determine the physiological role of this receptor. Crhr2-mutant mice are hypersensitive to stress and display increased anxiety-like behaviour. Mutant mice have normal basal feeding and weight gain, but decreased food intake following food deprivation. Intravenous Ucn produces no effect on mean arterial pressure in the mutant mice. [ABSTRACT FROM AUTHOR]

Abstract The availability of numerous genetically homogenous mouse strains permits the analysis of genetic influences on behavior and also behavioral sensitivity (responsivity) to drugs of abuse. The current study was conducted to characterize discriminated operant responding for food in four inbred strains (Balb/cByJ, DBA/2J, C57BL/6J, SJL/J), an F1 Hybrid (C57BL/6xSJL), and one outbred strain (CDI) of mouse. The effect of cocaine on this operant behavior was also examined. Initially, all animals were trained to nosepoke for food on a continuous reinforcement schedule. The minimum response requirement for reinforcement was increased every 5 days until the animals were responding on an FR-15 schedule of reinforcement. All strains increased operant responding as the schedule of reinforcement was raised. However, significant differences in response rate and discrimination learning were observed among the various strains of mice. Cocaine administration reduced operant responding for food in Balb/cByJ, C57BL/6J, C57BL/6xSJL/J and CDI mice at a dose of 15.0 mg/kg, whereas higher doses were required in DBA/2J mice (30.0 mg/kg) and SJL/J mice (56.0 mg/kg). These results suggest that operant performance and the effect of cocaine on this behavior is differentially influenced by genetic make-up. [ABSTRACT FROM AUTHOR]

Drug craving, the desire to experience the effect(s) of a previously experienced psychoactive substance, has been hypothesized to contribute significantly to continued drug use and relapse after a period of abstinence in humans. In more theoretical terms, drug craving can be conceptualized within the framework of incentive motivational theories of behavior and be defined as the incentive motivation to self-administer a psychoactive substance. The incentive-motivational value of drugs is hypothesized to be determined by a continuous interaction between the hedonic rewarding properties of drugs (incentive) and the motivational state of the organism (organismic state). In drug-dependent individuals, the incentive-motivational value of drugs (i.e., drug craving) is greater compared to non-drug-dependent individuals due to the motivational state (i.e., withdrawal) developed with repeated drug administration. In this conceptual framework, animal models of drug craving would reflect two aspects of the incentive motivation to self-administer a psychoactive substance. One aspect would be the unconditioned incentive (reinforcing) value of the drug itself. The other aspect would be relatively independent of the direct (unconditioned) incentive value of the drug itself and could be reflected in the ability of previously neutral stimuli to acquire conditioned incentive properties that could elicit drug-seeking and drug-taking behavior. Animal models of drug craving that permit the investigation of the behavioral and neurobiological components of these two aspects of drug craving are reviewed and evaluated. The models reviewed are the progressive ratio, choice, extinction, conditioned reinforcement and second-order schedule paradigms. These animal models are evaluated according to two criteria that are established herein as necessary and sufficient criteria for the evaluation of animal models of human psychopathology: reliability and predictive validity. The development of animal models of drug craving will have heuristic value and allow a systematic investigation of the neurobiological mechanisms of craving. [ABSTRACT FROM AUTHOR]

Buspirone and gepirone were evaluated as potential pharmacotherapies for cocaine abuse by studying the effects of acute and repeated treatment on IV cocaine self-administration in rhesus monkeys. Chlorpromazine was also evaluated as a positive control. Effects of IV drug pretreatments were tested during daily 60-min sessions with lever-pressing reinforced under a fixed-ratio 10 schedule of 0.02 or 0.05 mg/kg cocaine infusions. Acute pretreatment with buspirone (0.1 and 0.3 mg/kg, IV) increased rates of cocaine self-administration without disrupting food pellet consumption. Some doses of buspirone also produced changes in rates of cocaine self-administration without altering the within-session pattern of responding. In contrast, acute doses of gepirone had little effect on rates of cocaine self-administration, while disruptions in food consumption and changes in the within-session pattern of cocaine self-administration were obtained at the highest dose of gepirone tested (1.0 mg/kg). When either buspirone (0.1 and 0.3 mg/kg, IV) or gepirone (0.1 mg/kg, IV) were administered daily for 10 days, consistent effects on cocaine self-administration were not observed. Thus, the effects of acute buspirone administration on cocaine-maintained behavior were similar to the effects produced by chlorpromazine and other dopaminergic antagonists, whereas, gepirone was ineffective. These results provide some support for further evaluation of buspirone as a potential pharmacotherapy for cocaine abuse, although its lack of efficacy with repeated treatment is not encouraging. The negative results with gepirone provide less rationale for continued investigations with this drug, possibly because of its lesser involvement than buspirone with dopaminergic neurotransmission. [ABSTRACT FROM AUTHOR]

A series of experiments was conducted to assess the sensitivity of the acoustic startle response to chronic morphine administration and naloxone-precipitated withdrawal. Rats were implanted with two subcutaneous pellets containing either 75 mg each of morphine or containing only placebo. In experiment 1, withdrawal induced by 0.05-0.2 mg/kg naloxone dose-dependently decreased the magnitude of the startle response. Physical dependence was confirmed by a naloxone-induced acute weight loss seen in morphine-implanted rats, but naloxone had no effect on startle or body weight in nondependent animals. In experiment 2, a modified procedure with fewer trials per session and fewer test days was employed. Naloxone (0.2 mg/kg) given 4-5 days after implantation induced large startle-response decreases in morphine-dependent rats while having no effect in placebo-implanted rats. Post-naloxone saline tests revealed no significant differences in startle between morphine and placebo groups. Startle scores were significantly higher in morphine-implanted rats than in placebo rats during a saline test given 3 days following pellet implantation. In a separate group of animals, however, acute IP injections of morphine from 0.3-10 mg/kg had no significant effect on startle amplitude. The effect of repeated pairings of withdrawal with the startle environment was assessed in experiment 3. Morphine-dependent rats startled significantly less if naloxone injections were given before the startle session than if they were administered 4 h later. Conditioned withdrawal effects, expressed during a final test session when all rats received saline, were observed for the body-weight measure but not for the startle response. These results suggest that the acoustic startle response may be a useful objective measure in evaluating physical dependence produced by substances of abuse. [ABSTRACT FROM AUTHOR]

Derivatives of amphetamine are potent releasers of both dopamine (DA) and serotonin (5-HT), but the relative contributions of DA and 5-HT release to the behavioral effects of these drugs have not been established. Previously, S-(+)3,4-methylendioxymethamphetamine (S-(+)MDMA) was found to produce locomotor hyperactivity in rats which was dependent on 5-HT release. The present study found that MBDB (1.25, 2.5, 5.0 or 10.0 mg/kg), the alpha-ethyl derivative of MDMA that produces little or no direct DA release, also induced locomotor hyperactivity that lasted for greater than 60 min after the 5.0 and 10.0 mg/kg doses. MBDB produced spatial patterns of locomotor hyperactivity and suppression of exploratory activity (holepokes and rearings) very similar to the behavioral syndrome produced by MDMA. MBDB-induced hyperactivity was blocked by pretreatment with the selective 5-HT uptake inhibitor fluoxetine (2.5 or 10 mg/kg), suggesting that MBDB produced behavioral effects via uptake-carrier mediated release of 5-HT. Similarly, fluoxetine pretreatment blocked the locomotor hyperactivity produced by S-(+)3,4-methylenedioxyamphetamine (3.0 mg/kg) or p-chloroamphetamine (2.5 mg/kg), supporting a serotonergic basis for the action of these drugs. Tissue levels of 5-HT and its metabolite 5-HIAA were decreased 40 min after administration of S-(+)MDMA (3.0 mg/kg) or MBDB (5.0 mg/kg), and these decreases were prevented by fluoxetine pretreatment. S-(+)MDMA also produced a fluoxetine-sensitive increase of tissue DA levels, suggesting that 5-HT release may indirectly result in increased DA release, although MBDB did not significantly increase DA levels. These results point to a central role for 5-HT release in the stimulant-like behavioral effects of substituted derivatives of amphetamine. [ABSTRACT FROM AUTHOR]

Daily administration of a drug in a distinctive environment establishes contingencies that support Pavlovian conditioning. Environmental cues that are paired with the drug injection and that predict the onset of drug action can become conditioned stimuli. Ultimately, the conditioned stimuli come to predict the availability of drug and develop the potential to engender conditioned drug responses. Various psychostimulant drugs can produce conditioned locotnotion when tested in the presence of environmental cues that were repeatedly associated with the drug experience. The ability of amphetamine and cocaine to produce conditioned locomotion was demonstrated in the present study. Stimulant-like properties of methylenedioxymethamphetamine (MDMA) have been reported in locomotor paradigms, drug discrimination procedures, and human subjective questionnaires. MDMA (5 mg/kg), paired for 5 days to a distinct environment signalled by the presence of a distinct odor, produced enhanced locomotion during a test probe with the odor alone indicating that MDMA can also produce conditioned locomotion. The observation that the stimulus properties of MDMA can also become associated with environmental cues supports the hypothesis that some of the behavioral effects of MDMA resemble those of other classical psychostimulants such as amphetamine and cocaine. [ABSTRACT FROM AUTHOR]

Methylenedioxymethamphetamine (MDMA) is a phenylethylamine with a chemical structure that resembles both the amphetamines and mescaline and has both stimulant and perception altering properties. The stimulant properties of MDMA were assessed in photocell cages designed to measure locomotor activity in rats. MDMA, over a range of doses (2.5-10.0 mg/kg, SC) produced locomotor hyperactivity which lasted up to 4 h. Further studies examined the role of the mesolimbic dopamine system in the hyperactivity induced by MDMA. 6-Hydroxydopamine lesions of the Nucleus accumbens attenuated the locomotor response produced by MDMA. The well characterized attenuation of the locomotor response produced by amphetamine was also demonstrated in the same rats. The present study demonstrates similarities in the stimulant properties of MDMA and amphetamine, and also suggests that as with amphetamine, the locomotor activation associated with MDMA may involve the presynaptic release of dopamine in the region of the Nucleus accumbens. However, MDMA may have a more unusual pharmacological profile because of its longer duration of action, neurotoxic potential, and differences in the qualitative aspects of its psychoactive effects. [ABSTRACT FROM AUTHOR]

The influences of social status on amphetamine-induced behavioral effects in squirrel monkeys were investigated. Social status was determined by constructing a sociogram. d-Amphetamine (0.3-1.0 mg/kg orally, 0.3 and 0.6 mg/kg IM) increased stereotyped head movements and reduced the time spent in the sitting posture in all monkeys ( N=25) regardless of sex, age, or social status. The high levels of locomotor activity in dominant and juvenile monkeys were decreased at higher amphetamine doses (0.6 mg/kg IM, 0.6 and 1.0 mg/kg orally), whereas the same doses increased locomotion in otherwise less active subdominant and submissive animals. Low doses of amphetamine (0.1, 0.3 mg/kg) decreased the incidence of agonistic behavior initiated by dominant monkeys, and higher doses (0.6, 1.0 mg/kg) caused these monkeys to change from predominant initiators of agonistic behavior into recipients. At 2 h after amphetamine administration (0.3 mg/kg IM), the high levels of locomotor behavior had returned to baseline, the social isolation began to disappear, and the disrupted agonistic behavior of dominant monkeys returned to control levels, yet the stereotyped head movements continued to occur with high frequency. In half of the monkeys, amphetamine produced a large increase in distress-like vocalizations. Amphetamine-mediated motor stereotypies may be mediated by mechanisms different than those responsible for agonistic behavior. The selective changes in agonistic behavior by dominant monkeys when challenged with amphetamine may reflect a status-related functional alteration of catecholaminergic processes upon which the drug acts. [ABSTRACT FROM AUTHOR]

In the original publication of the article, the equation CHU9DPredicted = exp(BETAPrediction)∕(1 + exp(BETAPrediction)) was formatted incorrectly under Model 2. [ABSTRACT FROM AUTHOR]

Focuses on the use of hierarchical strategies for phenotypic analysis of the behavior of mice. Neurobehavioral protocols involved in phenotypic analysis in adult or neonatal mice; Procedures that can be used to evaluate the function of neural systems mediating motor output.