Cholinergic activation in frontal cortex and nucleus accumbens related to basic behavioral manipulations: handling, and the role of post-handling experience.

The present experiment is part of a series of studies designed to investigate cerebral cholinergic activity during basic behavioral testing procedures. Using in vivo microdialysis, we monitored extracellular acetylcholine levels in rats which were picked up manually (termed handling) and exposed to an open field, or animals which were picked up and returned to their home cage. These procedures were repeated on two consecutive days. In the lateral precentral area of the frontal cortex, both procedures increased cholinergic activity. However, on the 1 st day of testing, the degree of cholinergic activation was of even greater magnitude in animals which were returned to the home cage after handling than in animals which were exposed to a novel open field. This neurochemical pattern was dissociated from behavioral indices of activation, since rearing and locomotor activity were more pronounced in the open field than in the home cage. In the nucleus accumbens core and shell, where extracellular acetylcholine is provided by cholinergic interneurons, we also found cholinergic activation on both days of testing. However, unlike the frontal cortex, there were no substantial neurochemical differences between animals which were exposed to the open field after handling vs. those which were returned to their home cage. Together, our data suggest that a simple interaction like handling provides a significant stimulus for the animal to which cholinergic activity responds in several forebrain areas. Here, frontal cortical acetylcholine appears to be especially sensitive, with a pattern of activation which is dependent on post-handling experience. These results are discussed with respect to their possible functional implications, and the role of handling as an experimental factor. Since handling is part of many neurobehavioral procedures, handling-induced changes can interact with the imposed independent variables under investigation, such as post-trial pharmacological manipulations, requiring consideration in the interpretation of any experiment employing handling of the subjects. Copyright 1998 Elsevier Science B.V.