Selective breeding of 5-HT1A receptor-mediated responses: application to emotion and receptor action

Rat lines that were selectively bred for high (high DPAT-sensitive, HDS) or low (low DPAT-sensitive, LDS) hypothermic responses to the specific 5-HT1A receptor agonist, 8-hydroxy-di-n-propylaminotetralin (8-OH-DPAT), differ i n receptor binding and certain behaviors related to anxiety and depression. After reviewing this literature, the present communication summarizes new experiments designed to clarify and extend the nature of the pharmacologica l and biochemical differences between the lines. A challenge with the 5 HT2 receptor agonist, DOI, produced similar degrees of head shakes and skin cr awls in the HDS and LDS rats, suggesting similar sensitivity of 5-HT2A and 5-HT2C receptors. In contrast, DOI-induced flat body posture (FBP), which h as been linked to 5-HT1A receptor stimulation, was observed more readily in the HDS rats. The HDS and LDS rats exhibited similar degrees of increase i n 8-OH-DPAT-stimulated [S-35]GTP gammaS binding in several brain regions. T his result suggests that the dramatic differences in hypothermia in HDS and LDS rats cannot be related to 5-HT1A receptor-mediated action on G protein s. Overall, these findings indicate that the selective breeding for 5-HT1A- mediated hypothermia has been fairly selective, and that differences in emo tionally relevant behaviors between these two rat lines can strongly be ass ociated with an unidentified component of the 5-HT1A receptor signaling pat hway. (C) 2001 Elsevier Science Inc. All rights reserved.