Acetylcholine content and distribution in rat cortical synaptosomes after in vivo exposure to quinolinic acid.

In this study, changes in the concentration and subcellular distribution of rat cortical synaptosomal acetylcholine (ACh) was investigated after a single injection of quinolinic acid (QUIN) into the nucleus basalis magnocellularis (nbM). In the P2 fraction of normal animals the ACh concentration was 235 +/- 18 pmol/mg protein. Of this, 64 +/- 10% was recovered in the particulate (P3) fraction and 24 +/- 1% in the soluble (S3) fraction. Cortical synaptosomes (P2) prepared 0.5 h after injecting either 600 or 1000 nmol of QUIN contained significantly higher concentrations of ACh (372 +/- 127 and 496 +/- 77 pmol/mg protein, respectively) when compared to the amount of ACh in control animals. The ACh concentration in the P2 fraction was still elevated 3 h after injecting 600 nmol QUIN, however, synaptosomal ACh decreased significantly 3 h after rats were treated with 1000 nmol QUIN. Determination of subcellular ACh 0.5 h after injecting QUIN revealed that neither dose of QUIN produced a change in the distribution of ACh between P3 and S3. However, 3 h after injecting QUIN, a shift in the subcellular distribution of ACh to the cytoplasmic fraction (S3) was observed with 1000 nmol QUIN. These results show that QUIN-induced depolarization of nbM neurons which project to the cortex produce both dose-dependent and time-dependent changes in synaptosomal ACh concentration and subcellular distribution.