Commentary: Physician–Scientist's Frustrations Fester

Bloom, Floyd E.

doi:10.1038/npp.2008.181

Cited by 9 publications

(5 citation statements)

References 11 publications

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“…Furthermore, the doses of the psychostimulants, d-amphetamine, methamphetamine and MDMA used in this study did not modify the SWR behavior in the BTBR mice whereas MPTP reduced SWR activity in the control CB57BL/6J mice. One characteristic of ASDs is stereotype behavior characterized by high levels of repetitive self-grooming behavior that has recently been shown to be reduced in the BTBR mice by methyl-6-phenylethynl-pyridine (MPEP) – an mGluR5 antagonist [14]. It is tempting to suggest the evaluation of Δ 9 -THC or other cannabinoids with reduced psychoactivity in irritability, tantrums and self-injurious behavior associated with autistic individuals.…”

Section: Discussionmentioning

confidence: 99%

Consequences of Cannabinoid and Monoaminergic System Disruption in a Mouse Model of Autism Spectrum Disorders

Es¹,

Benno²,

Halpern³

et al. 2011

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Autism spectrum disorders (ASDs) are heterogenous neurodevelopmental disorders characterized by impairment in social, communication skills and stereotype behaviors. While autism may be uniquely human, there are behavioral characteristics in ASDs that can be mimicked using animal models. We used the BTBR T+tf/J mice that have been shown to exhibit autism-like behavioral phenotypes to 1). Evaluate cannabinoid-induced behavioral changes using forced swim test (FST) and spontaneous wheel running (SWR) activity and 2). Determine the behavioral and neurochemical changes after the administration of MDMA (20 mg/kg), methamphetamine (10 mg/kg) or MPTP (20 mg/kg). We found that the BTBR mice exhibited an enhanced basal spontaneous locomotor behavior in the SWR test and a reduced depressogenic profile. These responses appeared to be enhanced by the prototypic cannabinoid, Δ9-THC. MDMA and MPTP at the doses used did not modify SWR behavior in the BTBR mice whereas MPTP reduced SWR activity in the control CB57BL/6J mice. In the hippocampus, striatum and frontal cortex, the levels of DA and 5-HT and their metabolites were differentially altered in the BTBR and C57BL/6J mice. Our data provides a basis for further studies in evaluating the role of the cannabinoid and monoaminergic systems in the etiology of ASDs.

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Section: Discussionmentioning

confidence: 99%

Consequences of Cannabinoid and Monoaminergic System Disruption in a Mouse Model of Autism Spectrum Disorders

Es¹,

Benno²,

Halpern³

et al. 2011

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“…The nucleus accumbens, situated within the striatum, receives glutamatergic projections from the amygdala, hippocampus and prefrontal cortex and in turn sends GABAergic projections to the VTA, substantia nigra and ventral pallidum (Haber and Knutson, 2009, Haber et al ., 1990). This region is proposed to act in an integrative capacity assimilating goal directed information from the prefrontal cortex, environmental context from the hippocampus, and emotional significance from the amygdala to ultimately influence motor planning and action execution through its connections with the ventral pallidum and midbrain (Kalivas and Nakamura, 1999, Luo et al ., 2011, Mogenson and Yang, 1991).…”

Section: Anatomy Of Motivationmentioning

confidence: 99%

Oxytocin, motivation and the role of dopamine

Love

2014

Pharmacology Biochemistry and Behavior

292

216

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The hypothalamic neuropeptide oxytocin has drawn the attention of scientists for more than a century. The understanding of the function of oxytocin has expanded dramatically over the years from a simple peptide adept at inducing uterine contractions and milk ejection to a complex neuromodulator with a capacity to shape human social behavior. Decades of research have outlined oxytocin’s ability to enhance intricate social activities ranging from pair bonding, sexual activity, affiliative preferences, and parental behaviors. The precise neural mechanisms underlying oxytocin’s influence on such behaviors have just begun to be understood. Research suggests that oxytocin interacts closely with the neural pathways responsible for processing motivationally relevant stimuli. In particular, oxytocin appears to impact dopaminergic activity within the mesocorticolimbic dopamine system, which is crucial not only for reward and motivated behavior but also for the expression of affiliative behaviors. Though most of the work performed in this area has been done using animal models, several neuroimaging studies suggest similar relationships may be observed in humans. In order to introduce this topic further, this paper will review the recent evidence that oxytocin may exert some of its social-behavioral effects through its impact on motivational networks.

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“…Here, variation in rs4813625 was related to DA responses to a pain-stressor within the right ventromedial caudate. This region receives afferent projections from multiple limbic structures including the hippocampus, amygdala, orbitofrontal cortex and anterior cingulate (66) and is hypothesized to act in an integrative capacity, assimilating cognitive, affective and motivational information to influence behavioral action (66–68). We did not, however, observe any significant effects of OXT genotype on measures of pain sensitivity or changes in affective state during the pain challenge.…”

Section: Discussionmentioning

confidence: 99%

Oxytocin Gene Polymorphisms Influence Human Dopaminergic Function in a Sex-Dependent Manner

Love

Enoch

Hodgkinson

et al. 2012

Biological Psychiatry

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Background Oxytocin, classically involved in social and reproductive activities, is increasingly recognized as an antinociceptive and anxiolytic agent, effects which may be mediated via oxytocin’s interactions with the dopamine system. Thus, genetic variation within the oxytocin gene (OXT) is likely to explain variability in dopamine-related stress responses. As such, we examined how OXT variation is associated with stress-induced dopaminergic neurotransmission in a healthy human sample. Method Fifty-five young healthy volunteers were scanned using [11C] raclopride positron emission tomography while they underwent a standardized physical and emotional stressor that consisted of moderate levels of experimental sustained deep muscle pain, and a baseline, control state. Four haplotype tagging single nucleotide polymorphisms located in regions near OXT were genotyped. Measures of pain, affect, anxiety, well-being and interpersonal attachment were also assessed. Results Female rs4813625 C allele carriers demonstrated greater stress-induced dopamine release, measured as reductions in receptor availability from baseline to the pain-stress condition relative to female GG homozygotes. No significant differences were detected among males. We also observed that female rs4813625 C allele carriers exhibited higher attachment anxiety, higher trait anxiety and lower emotional well-being scores. In addition, greater stress-induced dopamine release was associated with lower emotional well-being scores in female rs4813625 C allele carriers. Conclusions Our results suggest that variability within the oxytocin gene appear to explain interindividual differences in dopaminergic responses to stress, which are shown to be associated with anxiety traits, including those linked to attachment style, as well as emotional well-being in women.

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Commentary: Physician–Scientist's Frustrations Fester

Cited by 9 publications

References 11 publications

Consequences of Cannabinoid and Monoaminergic System Disruption in a Mouse Model of Autism Spectrum Disorders

Consequences of Cannabinoid and Monoaminergic System Disruption in a Mouse Model of Autism Spectrum Disorders

Oxytocin, motivation and the role of dopamine

Oxytocin Gene Polymorphisms Influence Human Dopaminergic Function in a Sex-Dependent Manner

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