Time-dependent disruptive effects of apomorphine and alpha-methyl-p-tyrosine on development of morphine tolerance

Kesner, Raymond P.; Priano, D; Gold, Timothy

doi:10.1007/bf01457855

Cited by 4 publications

(1 citation statement)

References 17 publications

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“…3g). The dose of the drug and the testing time were chosen based on literature defining the time-and dose-dependent biochemical and behavioural effects of α-MPT 32,60,61 . After the behavioural tests, the mice were sacrificed by cervical dislocation.…”

Section: Methodsmentioning

confidence: 99%

Altered heparan sulfate metabolism during development triggers dopamine-dependent autistic-behaviours in models of lysosomal storage disorders

et al. 2021

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Lysosomal storage disorders characterized by altered metabolism of heparan sulfate, including Mucopolysaccharidosis (MPS) III and MPS-II, exhibit lysosomal dysfunctions leading to neurodegeneration and dementia in children. In lysosomal storage disorders, dementia is preceded by severe and therapy-resistant autistic-like symptoms of unknown cause. Using mouse and cellular models of MPS-IIIA, we discovered that autistic-like behaviours are due to increased proliferation of mesencephalic dopamine neurons originating during embryogenesis, which is not due to lysosomal dysfunction, but to altered HS function. Hyperdopaminergia and autistic-like behaviours are corrected by the dopamine D1-like receptor antagonist SCH-23390, providing a potential alternative strategy to the D2-like antagonist haloperidol that has only minimal therapeutic effects in MPS-IIIA. These findings identify embryonic dopaminergic neurodevelopmental defects due to altered function of HS leading to autistic-like behaviours in MPS-II and MPS-IIIA and support evidence showing that altered HS-related gene function is causative of autism.

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Section: Methodsmentioning

confidence: 99%