In vivo microdialysis was used to assess the effects of unilateral substance P (SP) injection into the nucleus basalis magnocellularis on extracellular levels of acetylcholine (ACh) in the frontal cortex, either in freely moving or urethane-anesthetized rats. The results show that the neurochemical effects of SP are critically dependent on the choice of the experimental preparation: In the freely-moving rat, the injection procedure led to behavioral and concurrent bilateral cholinergic activation in the frontal cortex. This cholinergic activation was ipsilaterally reduced by intrabasalis injection of SP (1 ng), indicating that the peptide exerted an inhibitory influence on the neurochemical effect exerted by handling, intracranial needle insertion, and vehicle injection. In the anesthetized preparation, SP had a biphasic dose-dependent action on cortical ACh: a short-lasting ipsilateral increase immediately after injection (especially with 1 ng), and a delayed bilateral increase after more than 2 h (10, 100 ng). The procedure of inserting the injection needle moderately increased cortical ACh levels. Methodologically, these data are discussed with respect to the importance of using anesthetized vs. freely moving rats and the effects of intraparenchymal injections.
Copyright 2000 Wiley-Liss, Inc.