Abstract: The objective of these experiments was to determine whether the chronic administration of nicotine, at a dose regimen that increases the density of nicotine binding sites, alters the nicotine-induced release of [
3H]dopamine ([
3H]DA), [
3H]norepinephrine ([
3H]NE), [
3H]serotonin ([
3H]5-HT), or [
3H]acetylcholine ([
3H]ACh) from rat striatal slices. For these experiments, rats received subcutaneous injections of either saline or nicotine bitartrate [1.76 mg (3.6 µmol)/kg, dissolved in saline] twice daily for 10 days, and neurotransmitter release was measured following preloading of the tissues with [
3H]DA, [
3H]NE, [
3H]5-HT, or [
3H]choline. Chronic nicotine administration did not affect the accumulation of tritium by striatal slices, the basal release of radioactivity, or the 25 m
M KCl-evoked release of neurotransmitter. Superfusion of striatal slices with 1, 10, and 100 µ
M nicotine increased [
3H]DA release in a concentration-dependent manner, and release from slices from nicotine-injected animals was significantly (
p < 0.05) greater than release from saline-injected controls; release from the former increased to 132, 191, and 172% of release from the controls following superfusion with 1, 10, and 100 µ
M nicotine, respectively. Similarly, [
3H]5-HT release increased in a concentration-related manner following superfusion with nicotine, and release from slices from nicotine-injected rats was significantly (
p < 0.05) greater than that from controls. [
3H]5-HT release from slices from nicotine-injected rats evoked by superfusion with 1 and 10 µ
M nicotine increased to 453 and 217%, respectively, of release from slices from saline-injected animals. The nicotine-induced release of [
3H]NE from striatal slices was also concentration dependent but was unaffected by chronic nicotine administration. [
3H]ACh release from striatal slices could not be detected when samples were superfused with nicotine but was measurable when tissues were incubated with nicotine. The release of [
3H]ACh from slices from nicotine-injected rats was significantly (
p < 0.05) less than release from controls and decreased to 36, 83, and 77% of control values following incubation with 1, 10, or 100 µ
M nicotine, respectively. This decreased [
3H]ACh release could not be attributed to methodological differences because slices from nicotine-injected rats incubated with nicotine exhibited an increased [
3H]DA release, similar to results from superfusion studies. In addition, it is unlikely that the decreased release of [
3H]ACh from striatal slices from nicotine-injected rats was secondary to increased DA release because [
3H]ACh release from slices from hippocampus, which is not tonically inhibited by DA, also decreased significantly (
p < 0.05) in response to nicotine; hippocampal slices from nicotine-injected rats incubated with 1 and 10 µ
M nicotine decreased to 42 and 70%, respectively, of release from slices from saline-injected animals. Results indicate that the chronic administration of nicotine increases the ability of nicotine to induce the release of [
3H]DA and [
3H]5-HT and decreases the ability of nicotine to evoke the release of [
3H]ACh but does not alter the nicotine-induced release of [
3H]NE from brain slices.
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