CONDITIONED TASTE-AVERSION PRODUCED BY CYCLOSPORINE-A - CONCOMITANT REDUCTION IN LYMPHOID ORGAN WEIGHT AND SPLENOCYTE PROLIFERATION

The classical conditioning of immune parameters is commonly conducted within a conditioned taste aversion (CTA) paradigm. In this study, the immunosuppressive drug cyclosporine A (CsA) was investigated for its ability to produce both taste aversion to a novel stimulus and conditi oned alterations in immune functioning. The paradigm comprised the pai ring of a 0.2% saccharin solution (the conditioned stimulus; CS) with an intraperitoneal injection of 20 mg/kg CsA (the unconditioned stimul us; UCS). Upon saccharin re-presentation, a marked reduction in fluid consumption was observed, indicating aversion to the novel substance ( =CTA). By using a single CsA/saccharin pairing the CTA lasted for one CS representation. However, by implementing three pairings, this effec t could be extended for up to seven representations. No noticeable dif ference was recorded by adjusting the saccharin representation from ev ery consecutive day to every second day. The most effective paradigm i n creating CTA was subsequently investigated for its effectiveness in producing conditioned immune alterations. Animals were killed on the d ay of the third CS re-presentation, and immune functions assessed. Con ditioned animals displayed a significant reduction in thymus and splee n weights. Effects on the spleen were further investigated, revealing a significantly reduced proliferative ability of isolated splenocytes to concanavalin A. These results demonstrate that the physiological ef fects produced by CsA are sufficiently salient to elicit CTA. Furtherm ore, the reduction in lymphoid organ weight and splenocyte proliferati on induced by CsA are also conditionable using this paradigm. (C) 1998 Elsevier Science Inc.