Changes in hippocampal morphology following chronic treatment with the synthetic cannabinoid WIN 55,212-2

Learning and memory are often correlated with cellular changes within the h ippocampus, and drugs or environmental factors which affect learning and me mory will thus often induce observable morphological changes in this struct ure. Like tetrahydrocannabinol (THC) itself, many synthetic cannabinoids su ch as the CB-1 receptor agonist WIN 55,212-2 will induce learning and memor y changes. In the current study, we investigate whether or not these change s could be related to structural changes within the hippocampus. Adult male Sprague-Dawley rats were injected twice daily (12:00 and 0:00 h) subcutane ously with WIN 55,212-2 (2.0 mg/kg) in DMSO or DMSO for 21 days. On day 22, animals were perfused and stained immunochemically for the dendritic marke r MAP-2, or with cresyl violet. Morphometric analysis showed dendritic rear rangement with increased staining of MAP-2 in CA3 and the lower blade of th e dentate gyrus. However, a loss of staining was observed in CA1. Counting of cresyl violet stained sections showed an apparent increase in granule ce ll number in the lower blade of the dentate gyrus. This work shows the pote ntial for cannabinoids to influence hippocampal morphology. The pattern of changes may be similar to that seen after ischemic or toxic damage, but may be opposite to changes seen in stress. (C) 2000 Elsevier Science B.V. All rights reserved.