A Comparison of Repeated MDMA- and AMPH-Produced Centre and Periphery Activity and the Underlying Neuroadaptations

<p>The recreational use of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') is increasing in New Zealand. MDMA is a ring-substituted derivative of AMPH and, similar to AMPH, produces hyperactivity upon administration. However, the behavioural profile of hyperlocomotion produced by MDMA differs from that produced by AMPH, suggesting that different neural mechanisms underlie the behavioural response. The repeated administration of both MDMA and AMPH induces sensitised hyperactive responses that have recently been found to be different. In the present study, MDMA- and AMPH-induced centre and periphery hyperactivity were compared to investigate the neuroadaptations produced by repeated exposure to the two drugs. Rats were pre-treated with saline, MDMA, or AMPH and the acute response to MDMA, AMPH, or the D1 agonist, SKF-81297 was measured to determine whether cross-sensitisation was produced. Repeated administration of MDMA and AMPH produced similar behavioural profiles. However, cross-sensitisation between the two drugs was uni-directional, suggesting that the two produce different neuroadaptations. Repeated AMPH, but not MDMA, produced a sensitised response to the hyperlocomotor effects of SKF-81297, suggesting that D1 receptor mechanisms are one example of different neuroadaptations.</p>

A Comparison of Repeated MDMA- and AMPH-Produced Centre and Periphery Activity and the Underlying Neuroadaptations

<p>The recreational use of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') is increasing in New Zealand. MDMA is a ring-substituted derivative of AMPH and, similar to AMPH, produces hyperactivity upon administration. However, the behavioural profile of hyperlocomotion produced by MDMA differs from that produced by AMPH, suggesting that different neural mechanisms underlie the behavioural response. The repeated administration of both MDMA and AMPH induces sensitised hyperactive responses that have recently been found to be different. In the present study, MDMA- and AMPH-induced centre and periphery hyperactivity were compared to investigate the neuroadaptations produced by repeated exposure to the two drugs. Rats were pre-treated with saline, MDMA, or AMPH and the acute response to MDMA, AMPH, or the D1 agonist, SKF-81297 was measured to determine whether cross-sensitisation was produced. Repeated administration of MDMA and AMPH produced similar behavioural profiles. However, cross-sensitisation between the two drugs was uni-directional, suggesting that the two produce different neuroadaptations. Repeated AMPH, but not MDMA, produced a sensitised response to the hyperlocomotor effects of SKF-81297, suggesting that D1 receptor mechanisms are one example of different neuroadaptations.</p>

Delayed Onset of Inhibition of Return in Visual Snow Syndrome

Visual snow syndrome (VSS) is a complex, sensory processing disorder. We have previously shown that visual processing changes manifest in significantly faster eye movements toward a suddenly appearing visual stimulus and difficulty inhibiting an eye movement toward a non-target visual stimulus. We propose that these changes reflect poor attentional control and occur whether attention is directed exogenously by a suddenly appearing event, or endogenously as a function of manipulating expectation surrounding an upcoming event. Irrespective of how attention is captured, competing facilitatory and inhibitory processes prioritise sensory information that is important to us, filtering out that which is irrelevant. A well-known feature of this conflict is the alteration to behaviour that accompanies variation in the temporal relationship between competing sensory events that manipulate facilitatory and inhibitory processes. A classic example of this is the “Inhibition of Return” (IOR) phenomenon that describes the relative slowing of a response to a validly cued location compared to invalidly cued location with longer cue/target intervals. This study explored temporal changes in the allocation of attention using an ocular motor version of Posner's IOR paradigm, manipulating attention exogenously by varying the temporal relationship between a non-predictive visual cue and target stimulus. Forty participants with VSS (20 with migraine) and 20 controls participated. Saccades were generated to both validly cued and invalidly cued targets with 67, 150, 300, and 500 ms cue/target intervals. VSS participants demonstrated delayed onset of IOR. Unlike controls, who exhibited IOR with 300 and 500 ms cue/target intervals, VSS participants only exhibited IOR with 500 ms cue/target intervals. These findings provide further evidence that attention is impacted in VSS, manifesting in a distinct saccadic behavioural profile, and delayed onset of IOR. Whether IOR is perceived as the build-up of an inhibitory bias against returning attention to an already inspected location or a consequence of a stronger attentional orienting response elicited by the cue, our results are consistent with the proposal that in VSS, a shift of attention elicits a stronger increase in saccade-related activity than healthy controls. This work provides a more refined saccadic behavioural profile of VSS that can be interrogated further using sophisticated neuroimaging techniques and may, in combination with other saccadic markers, be used to monitor the efficacy of any future treatments.

Adaptive aspects of impulsivity and interactions with effects of catecholaminergic agents in the 5-choice serial reaction time task: implications for ADHD

Background Work in humans has shown that impulsivity can be advantageous in certain settings. However, evidence for so-called functional impulsivity is lacking in experimental animals. Aims This study investigated the contexts in which high impulsive (HI) rats show an advantage in performance compared with mid- (MI) and low impulsive (LI) rats. We also assessed the effects of dopaminergic and noradrenergic agents to investigate underlying neurotransmitter mechanisms. Methods We tested rats on a variable inter-trial interval (ITI) version of the 5-choice serial reaction time task (5CSRTT). Rats received systemic injections of methylphenidate (MPH, 1 mg/kg and 3 mg/kg), atomoxetine (ATO, 0.3 mg/kg and 1 mg/kg), amphetamine (AMPH, 0.2 mg/kg), the alpha-2a adrenoceptor antagonist atipamezole (ATI, 0.3 mg/kg) and the alpha-1 adrenoceptor agonist phenylephrine (PHEN, 1 mg/kg) prior to behavioural testing. Results Unlike LI rats, HI rats exhibited superior performance, earning more reinforcers, on short ITI trials, when the task required rapid responding. MPH, AMPH and ATI improved performance on short ITI trials and increased impulsivity in long ITI trials, recapitulating the behavioural profile of HI. In contrast, ATO and PHEN impaired performance on short ITI trials and decreased impulsivity, thus mimicking the behavioural profile of LI rats. The effects of ATO were greater on MI rats and LI rats. Conclusions These findings indicate that impulsivity can be advantageous when rapid focusing and actions are required, an effect that may depend on increased dopamine neurotransmission. Conversely, activation of the noradrenergic system, with ATO and PHEN, led to a general inhibition of responding.

Like Mother Like Child: Do Fearful Sows Have Fearful Piglets?

Gestational and early life experiences affect subsequent behavioural and physical development. The objective of the current study was to investigate associations between gilts’ fear of humans, gestational stress level, and feeding and maternal behaviour, as well as how these related to aspects of the personality and growth of their offspring. A total of 37 gilts were used. Four human approach tests were performed between d 104 and d 111 of gestation to classify gilts as fearful or friendly. Gilt feeding behaviour and salivary cortisol concentration was measured between d 90 and d 108 of gestation, and gilt nursing behaviour assessed at d 13 of lactation. Piglets were subject to a back test at d 13 of age, to an open field test and a human approach test at d 20 of age, and growth was monitored to weaning (d 26 of age). Gilts classified as having a fearful behavioural profile had higher cortisol levels than friendly gilts (p < 0.05). Human fear level did not affect reproductive performance or the growth of offspring (p > 0.05). The offspring of friendly gilts tended to have a more active response to the back test (p = 0.09), less freezing response in the open field test (p < 0.05), and received human contact more than piglets from fearful gilts (p < 0.05). The present study shows that gilt human fear level is linked to their stress levels, which can affect the personality of their piglets.

Behavioural Concerns of Children on the Autism Spectrum and the Impact on Parental Quality of Life

PurposeThis study aimed to determine the association between parental quality of life (QoL) and autism severity, child’s cognitive level, adaptive behaviour and behavioural profile, and sociodemographic factors utilising the Quality of Life in Autism Questionnaire (QoLA).MethodsParents of children attending an autism specific preschool centre completed a sociodemographic questionnaire, the Quality of Life in Autism Questionnaire (QoLA), Vineland Adaptive Behaviour Scales 2nd edition (VABS) and Child Behaviour Checklist (CBCL). Trained researchers assessed autism severity with the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the cognitive level with the Mullen Scales of Early Learning (MSEL).ResultsFor parents of children on the autism spectrum, having other children without the condition buffered the potential negative effects on parental QoL. Lower levels of autism severity and internalising behaviours, and higher levels of daily living scores predicted greater perceived parental QoL. Parents perceived their child’s autism-specific behaviour as less problematic when the child had higher socialisation scores. While lower levels of Attention Problems, Withdrawn Behaviour and lower scores on the Dysregulation Profile (Externalising Behaviours, Aggressive Behaviour and Anxious/Depressed) predicted greater perceived parental QoL, higher levels of Withdrawn Behaviour, Aggression and Externalising Behaviour predicted poorer perceived parental QoL. There were no significant findings for the relationship between parental QoL and cognitive level.ConclusionThe present research establishes the complex effects of raising a child on the autism spectrum on parental QoL. Findings indicate a child’s autism symptom severity, adaptive functioning and behavioural profile has greater impact on parental QoL than cognitive level.

censusADHD Study: An Australian-wide medication-based recruitment study for Attention-Deficit/Hyperactivity Disorder

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) affects around 5% of children and is characterised by a persistent pattern of problems with focussing or maintaining attention and/or hyperactivity-impulsivity. The censusADHD Study is a richly-phenotyped nation-wide cohort of Australian children with ADHD that aims to examine the impact of children’s attention and behavioural problems on the financial, emotional, and psychological wellbeing of parents and caregivers. Methods: Families of potential ADHD cases aged between 6 and 11 years old were identified using Pharmaceutical Benefits Scheme (PBS) prescription records for ADHD medications held by the Department of Human Services and sent a study information letter. Data were collected from 1,574 primary caregivers via online survey from June-September 2015, including the behavioural profile of the index child, the child’s medication use and experiences with side-effects, and the impact of the child’s behaviour on the caregiver. Approximately 81% of caregivers also consented to record linkage of the child’s PBS and Medicare Benefits Schedule claims.Results: Boys were diagnosed with ADHD earlier (P=0.021) and more likely to present as the combined and predominantly hyperactive subtypes (P=0.001). Boys were also at higher risk for experiencing a school suspension (P&lt;0.001) or expulsion (P=0.043). Overall, children presenting as the combined subtype had higher rates of psychiatric comorbidities (P&lt;0.001). Finally, prescription costs for each family and the PBS significantly increased in the year following ADHD diagnosis (P&lt;0.001).Conclusion: Research examining the psychosocial and financial impact of ADHD on Australian children and their families in population-representative cohorts is needed. Our findings demonstrate the importance of examining both gender and ADHD subtype presentation in future studies.