Characterisation and autoradiographic localisation of 5-HT₃ receptor recognition sites identified with [³H]-(S)-zacopride in the forebrain of the rat

The pharmacological characterisation and topographical distribution of [³H]-(S)-zacopride recognition sites in the forebrain of the rat was studied using homogenate and autoradiographic radioligand binding techniques. [³H]-(S)-Zacopride labelled a single, saturable, specific binding site (defined by 10.0 μM granisetron) in homogenates prepared from the entorhinal cortex of the rat (pK_D = 9.5l ±0.08; B_max = 104 ± 7 fmolmg^-1 protein; mean ± SEM, n = 8). Pharmacological characterisatio of the recognition site, within the entorhinal cortex, suggested that [³H]-(S)-zacopride selectively labelled the recognition site of the 5-HT₃ receptor. Specific binding of [³H]-(S)-zacopride (defined by 1.0 μM granisetron) was differentially distributed throughout the forebrain of the rat; highest densities were located within sub-nuclei of the amygdala (cortical amygdaloid nucleus, amygdalohippocampal area, posterior medial cortical amygdaloid nucleus, posterior lateral amygdaloid nucleus), cortical areas (primary olfactory cortex, entorhinal cortex) and hippocampus. Non-specific binding was distributed homogeneously, although lower in myelinated structures. It is concluded that [³H]-(S)-zacopride selectively labels 5-HT₃ receptor recognition sites within the forebrain of the rat; the topographical distribution of these sites, within the limbic nuclei, is consistent with the behavioural actions in animal models of the selective 5-HT₃ receptor antagonists.