Imaging apomorphine stimulation of brain arachidonic acid signaling via D2-like receptors in unanesthetized rats.

Abstract:

RATIONALE AND OBJECTIVE:Because of the important role of dopamine in neurotransmission, it would be useful to be able to image brain dopamine receptor-mediated signal transduction in animals and humans. Administering the D1-D2 receptor agonist apomorphine may allow us to do this, as the D2-like receptor is reported to be coupled to cytosolic phospholipase A2 activation and arachidonic acid (AA) release from membrane phospholipid. METHODS:Unanesthetized adult rats were given intraperitoneally apomorphine (0.5 mg/kg) or saline, with or without pretreatment with 6 mg/kg intravenous raclopride, a D2/D3 receptor antagonist. [1-14C]AA was injected intravenously, then AA incorporation coefficients k*--brain radioactivity divided by integrated plasma radioactivity--markers of AA signaling, were measured using quantitative autoradiography in 62 brain regions. RESULTS:Apomorphine significantly elevated k* in 26 brain regions, including the frontal cortex, motor and somatosensory cortex, caudate-putamen, thalamic nuclei, and nucleus accumbens. Raclopride alone did not change baseline values of k*, but raclopride pretreatment prevented the apomorphine-induced increments in k*. CONCLUSIONS:A mixed D1-D2 receptor agonist, apomorphine, increased the AA signal by activating only D2-like receptors in brain circuits containing regions with high D2-like receptor densities. Thus, apomorphine might be used with positron emission tomography to image brain D2-like receptor-mediated AA signaling in humans in health and disease.

journal_title

Psychopharmacology

authors

Bhattacharjee AK,Chang L,White L,Bazinet RP,Rapoport SI

doi

10.1007/s00213-008-1073-3

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

557-66

issue

4

eissn

0033-3158

issn

1432-2072

journal_volume

197

pub_type

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