Autoradiographic localization of nicotinic receptor binding in rat brain using [³H]methylcarbamylcholine, a novel radioligand

Light microscopic autoradiography was used to visualize the neuroanatomical distribution of nicotinic receptors in rat brain using a novel radioligand, [³H]methylcarbamylcholine (MCC). Specific [³H]MCC binding to slide-mounted tissue sections of rat brain was saturable, reversible and of high affinity. Data analysis revealed a single population of [³H]MCC binding sites with a K_d value of 1.8 nM and B_max of 20.1 fmol/mg protein. Nicotinic agonists and antagonists competed for [³H]MCC binding sites in slide-mounted brain sections with much greater potency than muscarinic drugs. The rat brain areas containing the highest densities of [³H]MCC binding were in thalamic regions, the medial habenular nucleus and the superior colliculus. Moderate densities of [³H]MCC binding were seen over the anterior cingulate cortex, the nucleus accumbens, the zona compacta of substantia nigra and ventral tegmental area. Low densities of [³H]MCC binding were found in most other brain regions. These data suggest that [³H]MCC selectively labels central nicotinic receptors and that these receptors are concentrated in the thalamus, the medial habenular nucleus and the superior colliculus of the rat brain.