Striatal Nitric Oxide Activity Better Predicts Motor Disability Than Proto-Oncogenes

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Extrapyramidal symptoms (EPS) are known side effects of D2 antagonists and nitric oxide synthase (NOS) inhibitors.
• Previous research has not investigated NOS activity alongside c-Fos immunoreactivity (c-Fos-IR) after repeated dosing of these agents.

Purpose of the Study:

• To investigate the correlation between catalepsy and motor balance deficits with changes in c-Fos-IR, nNOS-positive cells, and NADPH-diaphorase activity in the striatum.
• To evaluate the effects of haloperidol (Hal), metoclopramide (MCP), and L-NOARG on these neurochemical markers.

Main Methods:

• Male Swiss mice were administered acute doses of Hal (0.1-1 mg/kg), MCP (1-45 mg/kg), L-NOARG (15-45 mg/kg), or saline.
• Behavioral tests included catalepsy assessment and the Rota-rod test for motor balance.
• Histochemical analysis quantified c-Fos-IR, nNOS-positive cells, and NADPH-diaphorase activity in the striatum.

Main Results:

• All tested drugs induced catalepsy; Hal and higher MCP doses impaired motor balance, while L-NOARG did not.
• Hal increased dorsal striatal c-Fos-IR; MCP increased c-Fos-IR in the dorsolateral striatum at specific doses.
• Both D2 antagonists increased dorsal striatal NADPH-diaphorase activity. L-NOARG also increased this activity but decreased c-Fos-IR in specific brain regions.

Conclusions:

• Acute administration of Hal, MCP, and L-NOARG induces catalepsy, but L-NOARG preserves motor balance.
• Findings suggest that NADPH-diaphorase activity in the dorsal striatum may be a key factor contributing to EPS.
• The study highlights differential effects of D2 antagonists and NOS inhibitors on striatal neurochemistry and behavior.