Nicotine binding to brain tissue from drug-naive and nicotine-treated rats.

Two nicotine binding sites with dissociation constants for nicotine of approximately 3 nM and 12 microM respectively have been found in homogenates of rat hippocampus, hypothalamus, parietal cortex and mesencephalon, the greatest density of high affinity binding sites being in parietal cortex (30.0 +/- 3.0 fmol (mg protein)-1), the lowest in hypothalamus (16.1 +/- 1.0 fmol (mg protein)-1). The density of the low affinity sites (approx. 20 pmol (mg protein)-1) did not show any regional variation. Neither site was present in homogenates of medulla oblongata. The accumulation of radioactivity following the subcutaneous administration of [3H]nicotine (0.4 mg kg-1) was rapid, the highest concentrations being found in the brain regions with the highest density of high affinity binding sites. Medulla oblongata did not accumulate radioactivity above the concentration found in plasma. The chronic administration of nicotine (0.4 mg kg-1 s.c. daily for 39 days) had no significant effects on [3H]nicotine binding to brain tissue or its accumulation into brain following subcutaneous administration. It is concluded that nicotine readily passes from plasma into brain tissue and is accumulated in the areas containing high affinity binding sites for the compound. It is also concluded that the biochemical and behavioural effects reported previously in response to the chronic daily administration of nicotine do not depend upon changes in its uptake or binding by brain tissue.