Phencyclidine affects firing activity of ventral tegmental area neurons that are related to reward and social behaviors in rats

Katayama, Tadahiro; Okamoto, Masahiro; Suzuki, Yoshiaki; Hoshino, Ken-Yo; Jodo, Eiichi

doi:10.1016/j.neuroscience.2013.02.047

Cited by 12 publications

(7 citation statements)

References 43 publications

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“…In contrast to studies in humans, research using animal models has consistently linked dysfunction in the mesolimbic dopaminergic reward pathway with atypical social function. For instance, both juvenile and adult animal models have demonstrated that (i) the NAc and VTA are responsive to social stimuli (Vanderschuren et al, 1995;Gordon et al, 2002;van Kerkhof et al, 2013); (ii) deficits in reciprocal social interactions arise from aberrant dopaminergic and glutamatergic neurotransmission (Katayama et al, 2013;Squillace et al, 2014;Bariselli et al, 2016;Krishnan et al, 2017); and (iii) that social play behaviour is modulated by dopaminergic signalling, in the mesolimbic reward pathway (Panksepp et al, 1984;Niesink and Van Ree, 1989;Manduca et al, 2016). A recent study used optogenetic manipulation of the mesolimbic reward pathway to show a causal role for this pathway in initiating and maintaining social interactions (Gunaydin et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…The mesolimbic reward pathway, which evaluates, regulates, and reinforces appetitive behaviours through dopaminergic signalling, is a core brain system for processing reward value (O'Connell and Hofmann, 2011). Although multiple studies using preclinical animal models of autism point to a link between aberrant mesolimbic reward pathway and dysfunction in reciprocal social interactions (Katayama et al, 2013;Gunaydin et al, 2014;Squillace et al, 2014;Bariselli et al, 2016;Krishnan et al, 2017), little is known about the integrity of this core reward circuit in ASD. Moreover, the relevance of findings in animal models to human clinical studies of childhood ASD remains largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

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Deficits in mesolimbic reward pathway underlie social interaction impairments in children with autism

Supekar

Kochalka

Schaer

et al. 2018

Brain

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Lack of interest in social interaction is a hallmark of autism spectrum disorder. Animal studies have implicated the mesolimbic reward pathway in driving and reinforcing social behaviour, but little is known about the integrity of this pathway and its behavioural consequences in children with autism spectrum disorder. Here we test the hypothesis that the structural and functional integrity of the mesolimbic reward pathway is aberrant in children with autism spectrum disorder, and these aberrancies contribute to the social interaction impairments. We examine structural and functional connectivity of the mesolimbic reward pathway in two independent cohorts totalling 82 children aged 7-13 years with autism spectrum disorder and age-, gender-, and intelligence quotient-matched typically developing children (primary cohort: children with autism spectrum disorder n = 24, typically developing children n = 24; replication cohort: children with autism spectrum disorder n = 17, typically developing children n = 17), using high angular resolution diffusion-weighted imaging and functional MRI data. We reliably identify white matter tracts linking-the nucleus accumbens and the ventral tegmental area-key subcortical nodes of the mesolimbic reward pathway, and provide reproducible evidence for structural aberrations in these tracts in children with autism spectrum disorder. Further, we show that structural aberrations are accompanied by aberrant functional interactions between nucleus accumbens and ventral tegmental area in response to social stimuli. Crucially, we demonstrate that both structural and functional circuit aberrations in the mesolimbic reward pathway are related to parent-report measures of social interaction impairments in affected children. Our findings, replicated across two independent cohorts, reveal that deficits in the mesolimbic reward pathway contribute to impaired social skills in childhood autism, and provide fundamental insights into neurobiological mechanisms underlying reduced social interest in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Deficits in mesolimbic reward pathway underlie social interaction impairments in children with autism

Supekar

Kochalka

Schaer

et al. 2018

Brain

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“…Elevated spike bursting of dopaminergic neurons presumably results in higher dopamine release and elevates the propensity for aberrant behaviours 39 . However, single unit measurements in freely moving (unanesthetized) mice are required to precisely assess the contribution of dopaminergic burst firing to neurobehavioral dysfunction 40 .…”

Section: Discussionmentioning

confidence: 99%

Perinatal Exposure to Neuregulin-1 Results in Disinhibition of Adult Midbrain Dopaminergic Neurons: Implication in Schizophrenia Modeling

Namba

Okubo

Nawa

2016

Sci Rep

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Aberrant neuregulin-1 (NRG1) signals are suggested to associate with the neuropathophysiology of schizophrenia. Employing a mouse schizophrenia model established by neonatal neuregulin-1 challenge, we analysed postpubertal consequence of the NRG1 pretreatment for the electrophysiological property of nigral dopamine neurons. In vivo single unit recordings from anaesthetized NRG1-pretreated mice revealed increased spike bursting of nigral dopamine neurons. In slice preparations from NRG1-pretreated mice, spontaneous firing was elevated relative to controls. The relative increase in firing rates was abolished by a GABAA receptor antagonist. Whole-cell recording showed that perinatal NRG1 pretreatment diminished inhibitory miniature synaptic currents as well as GABAA receptor sensitivity. These results collectively suggest that perinatal exposure to neuregulin-1 results in the disinhibition of nigral dopamine neurons to influence their firing properties at the adult stage when the behavioral deficits are evident.

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“…All natural behaviors, such as exploration of a space through locomotion (O'Keefe andDostrovsky, 1971) , vocalization (McCasland, 1987) , and social interactions (Katayama et al, 2013) are controlled by electrical activity in populations of neurons. Experiments in unrestrained, freely-moving animals have been key for understanding these neural control mechanisms.…”

Section: Recordings During Unrestrained Behaviormentioning

confidence: 99%

Welfare of zebra finches used in research

Yamahachi

Zai

Tachibana

et al. 2017

Preprint

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Over the past 50 years, songbirds have become a valuable model organism for scientists studying vocal communication from its behavioral, hormonal, neuronal, and genetic perspectives. Many advances in our understanding of vocal learning result from research using the zebra finch, a close-ended vocal learner. We review some of the manipulations used in zebra finch research, such as isolate housing, transient/irreversible impairment of hearing/vocal organs, implantation of small devices for chronic electrophysiology, head fixation for imaging, aversive song conditioning using sound playback, and mounting of miniature backpacks for behavioral monitoring. We highlight the use of these manipulations in scientific research, and estimate their impact on animal welfare, based on the literature and on data from our past and ongoing work. The assessment of harm-benefits tradeoffs is a legal prerequisite for animal research in Switzerland. We conclude that a diverse set of known stressors reliably lead to suppressed singing rate, and that by contraposition, increased singing rate may be a useful indicator of welfare. We hope that our study can contribute to answering some of the most burning questions about zebra finch welfare in research on vocal behaviors. Therefore, the interplay between corticosterone levels during development and long-term consequences of stress needs to be further studied. Skin temperatureA stressor can increase the core body temperature, provoking a decrease of the surface temperature. This phenomenon known as stress-induced hyperthermia could be utilized to measure stress. Indeed, infrared thermography has been used to determine the effect of stressful procedures in birds (Edgar et al., 2013;Herborn et al., 2015;Jerem et al., 2015) . Contrary to the stress snapshot of corticosterone, this non-invasive imaging method might provide longitudinal measurements of stress. Body weightBody weight can be used to assess body condition in birds, especially when multiple measurements are made over the course of a study (Brown, 1996;Dickens et al., 2009bDickens et al., , 2009a .

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Phencyclidine affects firing activity of ventral tegmental area neurons that are related to reward and social behaviors in rats

Cited by 12 publications

References 43 publications

Deficits in mesolimbic reward pathway underlie social interaction impairments in children with autism

Deficits in mesolimbic reward pathway underlie social interaction impairments in children with autism

Perinatal Exposure to Neuregulin-1 Results in Disinhibition of Adult Midbrain Dopaminergic Neurons: Implication in Schizophrenia Modeling

Welfare of zebra finches used in research

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