Protein kinase G linked to dopamine D3 receptors in the dorsal striatum controls dopamine release, ΔFosB expression and locomotor activity after repeated cocaine administration.

Abstract:

:Protein kinase G (PKG) has been implicated in a variety of physiological functions including synaptic plasticity in the brain. This study investigated the involvement of dopamine D3 (D3) receptors in PKG-regulated dopamine release, long-term changes in gene expression and behavioral sensitization after repeated cocaine administration. Repeated systemic injections of cocaine (20mg/kg), once a day for seven consecutive days, increased extracellular dopamine concentrations in the dorsal striatum. Inhibition of neuronal nitric oxide synthase, cGMP or PKG, stimulation of D3 receptors, and simultaneous inhibition of each of them with D3 receptor stimulation decreased the repeated cocaine-induced increase in dopamine concentrations and locomotor activity. Similarly, inhibition of PKG and simultaneous inhibition of PKG with D3 receptor stimulation decreased ΔFosB immunoreactivity elevated by repeated cocaine administration, however stimulation of D3 receptors alone did not. These findings suggest that activation of PKG after repeated cocaine administration is more sensitive to interact with D3 receptors in the dopamine terminals than those in medium spiny neurons. This interaction may result in the development of behavioral sensitization by the upregulation of dopamine releases in the dorsal striatum.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Lee DK,Oh JH,Yang JH,Youn B,Shim YB,Shim I,Wang JQ,Choe ES

doi

10.1016/j.neulet.2013.02.014

subject

Has Abstract

pub_date

2013-04-29 00:00:00

pages

120-5

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(13)00124-9

journal_volume

541

pub_type

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