DIFFERENTIAL REGULATION OF NEURONAL NICOTINIC RECEPTOR-BINDING SITES FOLLOWING CHRONIC NICOTINE ADMINISTRATION

Chronic nicotine administration to rats produces an increase in neuron al nicotinic receptors in the CNS. Moreover, the up-regulated sites la beled by [H-3]cytisine in cerebral cortex appear to be composed exclus ively of alpha 4 and beta 2 subunits. It is unknown whether receptor s ubtypes that do not bind [H-3]cytisine with high affinity are also aff ected. In the present studies, we tested the hypothesis that nicotine treatment differentially alters the density of neuronal nicotinic rece ptor subtypes in rat nervous tissues. Thus, we compared the binding of [H-3]cytisine with that of [H-3]epibatidine to nicotinic receptors in brain, spinal cord, and adrenal gland from rats that had been injecte d twice daily with nicotine or saline vehicle for 10 days. Chronic nic otine treatment led to an increase in nicotinic receptor binding sites in the cerebral cortex and in the dorsal lumbar spinal cord, but not in the thalamus. It is important that virtually all of the observed in creases could be accounted for by a selective effect on the fraction o f receptors exhibiting high affinity for both [H-3]cytisine and [H-3]e pibatidine. In contrast, no change in [H-3]epibatidine binding was see n in the adrenal gland, a tissue that does not exhibit high-affinity [ H-3]cytisine binding. These data indicate that, under the conditions u sed here, nicotine up-regulates the alpha 4 beta 2 nicotinic receptor subtype, which can be labeled by [H-3]cytisine and [H-3]epibatidine, b ut not non-alpha 4 beta 2 subtypes, which can be labeled by [H-3]epiba tidine.