Biomedical Engineering Reference
In-Depth Information
8
In Situ
Hybridization with Isotopic Riboprobes
for Detection of Striatal Neuropeptide
mRNA Expression After Dopamine
Stimulant Administration
Yasmin L. Hurd
1. Introduction
Stimulant drugs such as cocaine, amphetamine, and methylphenidate induce
their primary pharmacological actions through elevation of dopamine levels
in the brain. The most dense innervation of dopamine nerve terminals in the
central nervous system (CNS) is found within the striatum (caudate nucleus,
putamen, and nucleus accumbens)
(1)
. This brain region is central to the
wide range of actions of psychostimulant drugs on motor behavior, cognition,
motivation, and reward and is intricately linked with mesocorticolimbic
structures, also innervated by dopamine, such as the amygdaloid complex
and prefrontal cortex. The neuroanatomical organization and regulation of the
striatal dopaminergic system as well as its relevance to motor function and drug
reinforcement have been well studied. Elevation of striatal dopamine levels as
a consequence of psychostimulant drug administration leads to activation of
distinct dopamine receptor subtypes (D
1
-D
3
) that are differentially expressed
within distinct striatal neuronal populations. The predominant striatal cells are
medium spiny projection neurons (70-80%) and medium aspiny interneurons
(20-25%) that all contain the inhibitory neurotransmitter γ -aminobutyric acid
(GABA), but contain different neuropeptides. A major focus in regard to
stimulant effects in the striatum has been directed toward the medium spiny
neurons that not only have distinct neuropeptidergic content, but also discrete
efferent anatomical connectivity. Medium spiny neurons in the dorsal striatum
that contain the opioid peptide dynorphin and the tachykinin substance P
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