CHRONIC NICOTINE ADMINISTRATION DIFFERENTIALLY AFFECTS NEUROTRANSMITTER RELEASE FROM RAT STRIATAL SLICES

The objective of these experiments was to determine whether the chroni c administration of nicotine, at a dose regimen that increases the den sity of nicotine binding sites, alters the nicotine-induced release of [H-3]dopamine ([H-3]DA), [H-3]norepinephrine ([H-3]NE), [H-3]serotoni n ([H-3]5-HT), or [H-3]acetylcholine ([H-3]ACh) from rat striatal slic es. For these experiments, rats received subcutaneous injections of ei ther saline or nicotine bitartrate [1.76 mg (3.6 mu mol)/kg, dissolved in saline] twice daily for 10 days, and neurotransmitter release was measured following preloading of the tissues with [H-3]DA, [H-3]NE, [H -3]5-HT, or [H-3]choline. Chronic nicotine administration did not affe ct the accumulation of tritium by striatal slices, the basal release o f radioactivity, or the 25 mM KCI-evoked release of neurotransmitter. Superfusion of striatal slices with 1, 10, and 100 mu M nicotine incre ased [H-3]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 f ollowing superfusion with 1, 10, and 100 mu M nicotine, respectively. Similarly, [H-3]5-HT release increased in a concentration-related mann er following superfusion with nicotine, and release from slices from n icotine-injected rats was significantly (p < 0.05) greater than that f rom controls. [H-3]5-HT release from slices from nicotine-injected rat s evoked by superfusion with 1 and 10 mu M nicotine increased to 453 a nd 217%, respectively, of release from slices from saline-injected ani mals. The nicotine-induced release of [H-3]NE from striatal slices was also concentration dependent but was unaffected by chronic nicotine a dministration. [H-3]ACh release from striatal slices could not be dete cted when samples were superfused with nicotine but was measurable whe n tissues were incubated with nicotine. The release of [H-3]ACh from s lices from nicotine-injected rats was significantly (p < 0.05) less th an release from controls and decreased to 36, 83, and 77% of control v alues following incubation with 1, 10, or 100 mu M nicotine, respectiv ely. This decreased [H-3]ACh release could not be attributed to method ological differences because slices from nicotine-injected rats incuba ted with nicotine exhibited an increased [H-3]DA release, similar to r esults from superfusion studies. In addition, it is unlikely that the decreased release of [H-3]ACh from striatal slices from nicotine-injec ted rats was secondary to increased DA release because [H-3]ACh releas e from slices from hippocampus, which is not tonically inhibited by DA , also decreased significantly (p < 0.05) in response to nicotine; hip pocampal slices from nicotine-injected rats incubated with 1 and 10 mu M nicotine decreased to 42 and 70%, respectively, of release from sli ces from saline-injected animals. Results indicate that the chronic ad ministration of nicotine increases the ability of nicotine to induce t he release of [H-3]DA and [H-3]5-HT and decreases the ability of nicot ine to evoke the release of [H-3]ACh but does not alter the nicotine-i nduced release of [H-3]NE from brain slices.