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 inve stigate cerebral cholinergic activity during basic behavioral testing procedures. Using in vivo microdialysis, we monitored extracellular ac etylcholine levels in rats which were picked up manually (termed handl ing) and exposed to an open field, or animals which were picked up and returned to their home cage. These procedures were repeated on two co nsecutive days. In the lateral precentral area of the frontal cortex, both procedures increased cholinergic activity. However, on the 1 st d ay of testing, the degree of cholinergic activation was of even greate r magnitude in animals which were returned to the home cage after hand ling than in animals which were exposed to a novel open field. This ne urochemical pattern was dissociated from behavioral indices of activat ion, since rearing and locomotor activity were more pronounced in the open field than in the home cage. In the nucleus accumbens core and sh ell, where extracellular acetylcholine is provided by cholinergic inte rneurons, we also found cholinergic activation on both days of testing . However, unlike the frontal cortex, there were no substantial neuroc hemical differences between animals which were exposed to the open fie ld after handling vs. those which were returned to their home cage. To gether, our data suggest that a simple interaction Like handling provi des a significant stimulus for the animal to which cholinergic activit y responds in several forebrain areas. Here, frontal cortical acetylch oline appears to be especially sensitive, with a pattern of activation which is dependent on post-handling experience. These results are dis cussed 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 interac t with the imposed independent variables under investigation, such as post-trial pharmacological manipulations, requiring consideration in t he interpretation of any experiment employing handling of the subjects . (C) 1998 Elsevier Science B.V. All rights reserved.