D1 Receptor Functional Asymmetry at Striatonigral Neurons: A Neurochemical and Behavioral Study in Male Wistar Rats

J Neurosci Res. 2025 Jan;103(1):e70014. doi: 10.1002/jnr.70014.

Abstract

Lateralization of motor behavior, a common phenomenon in humans and several species, is modulated by the basal ganglia, a site pointed out for the interhemispheric differences related to lateralization. Our study aims to shed light on the potential role of the striatonigral D1 receptor in functional asymmetry in normal conditions through neurochemical and behavioral means. We found that D1 receptor activation and D1/D3 receptor coactivation in striatonigral neurons leads to more cAMP production by adenylyl cyclase in the striatum and GABA release in their terminals in the right hemisphere compared to the left. These differences are linked to a higher receptor sensitivity and potentially a better coupling of Golf proteins. When we assessed motor behavior through intranigral injection of the D1 receptor agonist SKF 38393 in the left or right substantia nigra, we found higher contralateral circling when injected on the right side. Thus, differences in motor activity correlate with neurochemical data, indicating that D1 receptor signaling plays a significant role in motor asymmetry.

Keywords: D1 receptor; D3 receptor; asymmetry; motor behavior; striatonigral neurons.

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Animals
  • Corpus Striatum* / drug effects
  • Corpus Striatum* / metabolism
  • Cyclic AMP / metabolism
  • Dopamine Agonists / pharmacology
  • Functional Laterality* / drug effects
  • Functional Laterality* / physiology
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neurons* / drug effects
  • Neurons* / metabolism
  • Rats
  • Rats, Wistar*
  • Receptors, Dopamine D1* / agonists
  • Receptors, Dopamine D1* / metabolism
  • Substantia Nigra* / drug effects
  • Substantia Nigra* / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Receptors, Dopamine D1
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Dopamine Agonists
  • gamma-Aminobutyric Acid
  • Cyclic AMP