Investigating the Influence of Morphine and Cocaine on the Mesolimbic Pathway Using a Novel Microimaging Platform

Int J Mol Sci. 2023 Nov 14;24(22):16303. doi: 10.3390/ijms242216303.

Abstract

Dopamine (DA)'s relationship with addiction is complex, and the related pathways in the mesocorticolimbic system are used to deliver DA, regulating both behavioral and perceptual actions. Specifically, the mesolimbic pathway connecting the ventral tegmental area (VTA) and the nucleus accumbens (NAc) is crucial in regulating memory, emotion, motivation, and behavior due to its responsibility to modulate dopamine. To better investigate the relationship between DA and addiction, more advanced mapping methods are necessary to monitor its production and propagation accurately and efficiently. In this study, we incorporate dLight1.2 adeno-associated virus (AAV) into our latest CMOS (complementary metal-oxide semiconductor) imaging platform to investigate the effects of two pharmacological substances, morphine and cocaine, in the NAc using adult mice. By implanting our self-fabricated CMOS imaging device into the deep brain, fluorescence imaging of the NAc using the dLight1.2 AAV allows for the visualization of DA molecules delivered from the VTA in real time. Our results suggest that changes in extracellular DA can be observed with this adapted system, showing potential for new applications and methods for approaching addiction studies. Additionally, we can identify the unique characteristic trend of DA release for both morphine and cocaine, further validating the underlying biochemical mechanisms used to modulate dopaminergic activation.

Keywords: CMOS imaging; NAc; VTA; cocaine; dLight AAV; dopamine; fluorescence imaging; morphine.

MeSH terms

  • Animals
  • Cocaine*
  • Dopamine / metabolism
  • Mice
  • Morphine / metabolism
  • Morphine / pharmacology
  • Nucleus Accumbens / metabolism
  • Ventral Tegmental Area / metabolism

Substances

  • Cocaine
  • Dopamine
  • Morphine

Grants and funding

This work was, in part, supported by JSPS Fostering Joint International Research (B), grant number 22KK0180 from the Ministry of Education, Science, Sports. This study is also partially supported by a fund from the University of Houston.