Variations in maternal behavior in the rat as a function of sex and gonadal state

Performance of major components of maternal care was evaluated quantitatively in several test situations for various groups of rats. Maternal behavior of concaveated ovaríectomized virgin females and castrated males was inferior on a variety of measures to that of concaveated intact virgin females. However, concaveated intact virgin females were markedly inferior to natural mothers on measures of nest building and responsiveness to an intruder. Thus, it was found that test situations other than the standard homecage test revealed previously undetected group differences and that the occurrence of pup retrieval is not a valid predictor of the performance of some major components of maternal care. In addition, it was concluded that gonadal hormones partially determine the quality of maternal responsiveness displayed by virgin females, but that gonadal hormones characteristic of the cycling female are not sufficient to increase maternal responsiveness to the level seen with natural mothers. Possible relationships between pup-induced maternal behavior and that of natural mothers are discussed.     

Synthesis of oxytocin derivatives lipidated via a carbonate or carbamate linkage as a long-acting therapeutic agent for social impairment-like behaviors

In the course of our studies of hydrophobic oxytocin (OT) analogues, we newly synthesized lipidated OT (LOT-4a-c and LOT-5a-c), in which a long alkyl chain (C14-C16) is conjugated via a carbonate or carbamate linkage at the Tyr-2 phenolic hydroxy group and a palmitoyl group at the terminal amino group of Cys-1. These LOTs did not activate OT and vasopressin receptors. Among the LOTs, however, LOT-4c, having a C16-chain via a carbonate linkage at the phenolic hydroxyl group of the Tyr-2, showed very long-lasting action for the recovery of impaired social behavior in CD38 knockout mice, a rodent model of autistic phenotypes, whereas the effect of OT itself rapidly diminished. These results indicate that LOT-4c may serve as a potential prodrug in mice.