In this study, we compared the localization of central 5-HT, binding sites of rat and guinea pig. The 5-HT1B sites were absent in the guinea pig brain. Good correlations were found between species in the regional distribution of 5-HT1 sites labelled with [H-3]5-HT (r = 0.73), 5-HT1A sites labelled with [H-3]8-OH-DPAT (r = 0.87), and 5-HT1B versus 5-HT1D sites labelled with [H-3]5-HT in the presence of ipsapirone and DOI (r = 0.76). Despite the overall similarities, species differences were observed in many brain regions. The CA1/CA2 fields of the hippocampus and the dorsal subiculum displayed significantly more 5-HT1A receptor binding in guinea pig than in rat. Conversely, the 5-HT1A binding in dorsolateral septum, cingulate cortex and laminae IV-V of the neocortex, was more pronounced in rat. Areas almost exclusively containing 5-HT1B or 5-HT1D, sites, such as the ventral pallidum, globus pallidus and substantia nigra, expressed markedly more [H-3]5-HT binding in rat as compared to guinea pig, while the opposite occurred in claustrum, dorsal endopiriform nucleus, lateral geniculate nucleus, and superficial grey layer of the superior colliculus. The implications of the species differences are illustrated by the binding of [H-3]eltoprazine. The distribution of [H-3]eltoprazine binding sites showed a good correlation with that of the 5-HTIB sites in rat (r = 0.89), and with that of the 5-HT1A sites in guinea pig (r = 0.97). The data give rise to the possibility that differences in the presence and distribution of 5-HT1 receptor sites are related to species differences in behavioural, neurochemical and physiological responses to drugs with 5-HT1 receptor affinity.
