 1997 John Wiley & Sons, Inc. CCC 0012-1630/97/040255-11 Susan A. Brunelli Danielle D. Vinocur D orene Soo-H oo Myron A. Hofer College of Physicians and Surgeons Columbia University and Developmental Psychobiology New York State Psychiatric Institute New York, NY 10032 Five Generations of Selective Breeding for Ultrasonic Vocalization (U SV ) Responses in Strain Rats N :NIH Received 27 June 1996; accepted 2 January 1997 ABSTRACT: This article reports on early results from an ongoing selective breeding study in which rats were selected for different rates of ultrasonic vocalization (USV) in response to isolation. Using the strain, all litters were screened at 10 (1) days of age in a 2-min N : NIH isolation test, and those males and females with the highest (or lowest) rates in each litter were selected for later breeding with like breeders from unrelated litters. A Random line (unselected control) was also bred. In the first selected generation (S1), the Low line diverged from Random line controls, and has maintained significantly lower rates over all generations since. In the S3 generation, the High line diverged significantly from Random line controls, and has shown significantly higher USV rates in each succeeding generation. No line differences were found in other behaviors measured in isolation. Data from a small sample of S5 pups tested at postnatal Days 3, 10, 14, and 18 days showed that individual pups’ rates of USV from Day 10 predicted those at Day 14, consistent with findings from an unselected generation. Ambient temperature, modulated by body weight, controlled USV at Day 3, whereas at Days 10 and 14 line accounted for most of the variance in USV. This is the first instance of laboratory selection occurring on the basis of an infantile trait.  1997 John Wiley & Sons, Inc. Dev Psychobiol 31: 255–265, 1997 Keywords: rats; ultrasonic vocalization; development; isolation; anxiety; selective N : NIH breeding; USV Selective breeding for a differential behavioral re- sponse (in which the average rates of a behavioral phenotype are pushed in opposite directions in two separately bred lines) is a powerful tool to study mech- anisms underlying those phenotypes (Deitrich, 1993). Some examples of how selective breeding is used in this way are studies in which rodents are bred for a Correspondence to: S. A. Brunelli Contract grant sponsor: NIMH Contract grant number: MH 40430– 09 Contract grant sponsor: NYS Psychiatric Institute Contract grant number: 903-8604B variety of responses to alcohol. Thus lines of rats have been selectively bred for differential responses to al- cohol such as sensitivity to ethanol, acute and chronic tolerance, hypothermia, and ataxia. Each of these stud- ies have selected phenotypes that shed light on behav- ioral and physiologic mechanisms underlying suscep- tibility to alcohol addiction (Crabbe & Belknap, 1992; Crabbe & Phillips, 1993; Deitrich, 1993; Li, Lumeng, & Doolittle, 1993). To examine processes underlying generational and developmental influences on anxiety in an animal model (Hofer, 1996; Miczek, Tornatsky, & Vivian,