Three groups of female Sprague-Dawley rats (n=4) were conditioned to drink water during a daily 2 hr session. The water was then changed to a solution of 1.0 mg/ml lithium chloride producing average doses between 62.9 and 72.1 mg/kg/day for Groups I and II. These rats were challenged with 4 mg/kg PCP i.p. before and during lithium treatment. Group I was tested for spontaneous locomotor activity in the open field apparatus. Lithium alone did not affect activity. After 1, 2, and 3 weeks of chronic lithium, PCP-induced activity increased 2.1, 1.7, and 2.8 fold, respectively, relative to PCP-induced activity during limited access to water only. Whole brain homogenates from Group II, after one week of chronic lithium, were used for receptor binding experiments using [3H] PCP; Group III served as water controls. The Kd (nM ± S.E.M.) was not different in untreated (146.39 ± 18.95) and lithium-treated (181.22 ± 14.35) rats. The Bmax (pmole/mg protein ± S.E.M.), however, was increased 48% (p < 0.01) from 1.50 ± 0.08 to 2.22 ± 0.10 after lithium. These preliminary results suggest that chronic administration of lithium modifies the behavioral effects of PCP possibly via alterations at the receptor level.
Bibliographical noteFunding Information:
The authors wish to express their appreciation to Ms. Nancy Goodman for determining lithium concentrations, to Mr. Michael A. Gentry for technical assistance, and to Ms. Anita Saulsbury and Ms. Pat Tretter for preparation of this manuscript. This work was supported by NIDA grant DA-03173, and U. S. Army contract DAAK11-84-O001).
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