Decision time and perseveration of adolescent rats in the T-maze are affected differentially by buspirone and independent of 5-HT-1A expression

Abstract

Disruption of spontaneous alternation behavior (SAB) by the serotonin 1A (5-HT-1A) receptor agonist, 8-hydroxy-dipropylaminotetraline (8-OH-DPAT), results in repetitive behaviors that have been used to model the perseveration and indecisiveness of human obsessive-compulsive disorder (OCD). In the present study, we compared the effects of buspirone to those of 8-OH-DPAT in two strains of adolescent rats and analyzed repetitive choices of arms of the maze and prolonged apparent decision time due to induction of vicarious trial and error (VTE) behavior. In adolescent Sprague–Dawley (SD) rats, 8-OH-DPAT induced repetitive choices of arms of the maze (perseveration) and increased the apparent decision time. Buspirone induced VTE behavior and increased apparent decision time without perseveration. This distinct effect of buspirone was seen in SD adolescents but not in Long-Evans (LE) adolescents which appeared to be insensitive to buspirone. Lack of responsiveness to buspirone was dependent on the developmental stage because buspirone induced VTE behavior and prolonged decision time in LE adults. Western blotting of brain 5-HT-1A receptors showed expression of receptor protein in adolescent LE brain was comparable to that of adolescent SD and adult LE. The 5-HT-1A antagonist WAY 100365 blocked the effect 8-OH-DPAT on repetitive choice of arms but not the effect of buspirone on VTE behavior. We conclude that the adolescent LE rat has normal levels of 5-HT-1A receptor and that the effect of buspirone on VTE behavior is not mediated by the 5-HT-1A receptor. The LE strain may provide a useful system for further study of the adolescent brain and potential genetic differences in induction of repetitive behaviors.