[Abstract Title]. - Society for Neuroscience

Title: Dopaminergic modulation of nitric oxide synthase activity in the nucleus accumbens:
Histochemical analysis of regional subdivisions
Authors: *K. E. HOQUE, R. P. INDORKAR, S. SAMMUT, A. R. WEST;
Rosalind Franklin Univ., North Chicago, IL
Abstract: The integration of motivational processes within limbic and basal ganglia circuits is
vital for normal cognition and goal-directed behavior. The nucleus accumbens (NAc) serves as
an essential functional interface between these two systems. Nitric oxide (NO) is a gaseous
neurotransmitter synthesized by aspiny interneurons containing neuronal NO synthase (nNOS).
nNOS activity in the striatal complex can be detected with NADPH-diaphorase staining, a
histochemical technique that utilizes the NADPH reducing activity of nNOS in fixed tissue.
nNOS activation in the striatal complex is believed to be NMDA receptor dependent and
regulated by activation of dopamine D1 and D2 like receptors. In this study, nNOS activity was
determined using optical density measures of NADPH-diaphorase staining preformed in
subdivisions (core, medial shell, intermediate shell and lateral shell) of the NAc. Awake
behaving rats received i.p. injections of either saline, the D1 receptor agonist SKF 81297, the D1
receptor antagonist SCH 23390 followed by SKF 81297, or the nNOS inhibitor N G -propyl-Larginine
(NPA) followed by SKF 81297, approximately 25 minutes prior to harvesting the brain
for staining and analysis. In saline treated animals a distinct medial-lateral histochemical
gradient of NADPH-diaphorase staining was observed. This gradient was characterized by
moderate NADPH-diaphorase staining in the core and medial shell and robust staining in the
intermediate and lateral shell which was approximately three-fold higher than more medial
subregions. SKF 81297 administration preferentially increased NADPH-diaphorase staining twofold
in the medial shell. Pretreatment with both SCH 23390 and NPA attenuated the SKF 81297induced
increase in NADPH-diaphorase staining in the medial shell and decreased staining in the
intermediate shell as compared to saline controls. These observations demonstrate that nNOS
activity measured in regionally distinct populations of NOS interneurons in the NAc is
differentially modulated by D1 receptor activation. Similar studies assessing the impact of
glutamatergic and D2 receptor activation on nNOS activity in NAc subregions are ongoing.
Further characterization of the regulation of NOS activation in NAc subregions may facilitate the
development of novel pharmacotherapies for treating disorders of cognition and motivation.
Disclosures: K.E. Hoque, None; R.P. Indorkar, None; S. Sammut, None; A.R. West, None.
Poster
273. Basal Ganglia: Transmitters and Neuromodulation I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 273.3/II18