2-NAP, a peripheral CCK-A receptor antagonist, modulates the development of a preference for the mother by the newborn lamb

The aim of this study was to investigate the effect of devazepide (DEV), a cholecystokinin (CCK)-A receptor antagonist, which crosses the blood-brain barrier (BBB) and prevents the development of a preferential relationship with the dam, and compare it to that of 2-NAP, which acts peripherally. At birth, lambs received either an intraperitoneal injection of saline (CTL), DEV (0.1 mg/kg), or 2-NAP (0.01, 0.1, or 1 mg/kg). No major side effects were observed after the injection, however, there was a trend for lambs receiving CCK-A antagonists to be more vocal in the first 2 h and to loose more weight between birth and 3 h. When tested in a two-choice test situations at 24 h of age, the latency to reach a ewe and the total time spent next to them were not affected by the treatments. On the other hand, unlike CTLs, lambs receiving DEV or 0.1 mg of 2-NAP did not spend significantly more time near their dam than near the alien ewe. 2-NAP had no effect at 0.01 mg/kg, but at 1 mg/kg, it improved the preference score. There was no relationship between preference scores and the variations in weight recorded during the neonatal period. The effects of DEV, but not those of 2-NAP, persisted at 48 h of age. Thus, these results support the hypothesis that peripheral CCK receptors are involved in the development of a preference for the mother, but the effects differ according to the amount of 2-NAP that the lambs receive. (C) 2000 Elsevier Science Inc. All rights reserved.