Opposed Behavioural Outputs of Increased Dopamine Transmission in Prefrontocortical and Subcortical Areas: A Role for...

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Psychopharmacology

Background:

• Previous studies suggested dopamine in the medial prefrontal cortex (mPFC) inhibits locomotor behavior, but evidence was indirect.
• Prior research primarily used permanent dopamine depletion, limiting the understanding of acute dopamine function.

Purpose of the Study:

• To provide direct evidence for the inhibitory role of medial prefrontal cortex (mPFC) dopamine on locomotor activity.
• To investigate the specific dopamine receptor subtype involved in this inhibitory pathway.

Main Methods:

• Rats received local injections of amphetamine into the mPFC to acutely increase dopamine transmission.
• Locomotor activity was assessed following mPFC amphetamine administration.
• The effects of intra-mPFC injections of the D-1 dopamine receptor antagonist SCH-23390 on locomotion were examined, alongside other dopamine receptor antagonists.

Main Results:

• Acute increases in dopamine transmission in the mPFC by amphetamine injections inhibited the locomotor-activating effects of amphetamine in the nucleus accumbens (N.Acc.).
• Intra-mPFC administration of SCH-23390, a D-1 dopamine receptor antagonist, enhanced locomotion induced by intra-N.Acc. amphetamine.
• Other dopamine antagonists with different receptor affinities did not produce this enhancement, indicating D-1 receptor specificity.

Conclusions:

• These findings provide direct evidence that dopamine acting in the mPFC inhibits locomotor activity.
• The results strongly suggest that this inhibitory effect is mediated via D-1 dopamine receptors within the mPFC.