Effects of lithium and neuroleptics and combinations of the two on renal function and structure in rats

The effects of 8 weeks of treatment with lithium and neuroleptics, alone and combined, on renal concentrating ability and morphology were studied in rats. LiCl was administered in the diet and neuroleptics were given as one daily dose: haloperidol 1 mg/kg, chlorpromazine 15 mg/kg, and perphenazine 4 mg/kg. Plasma lithium levels were about 1 mmol/l, and the area under the plasma concentration curve was not statistically different in the control and neuroleptic groups. Rats treated with lithium developed marked polyuria which was less in rats receiving neuroleptics concomitantly. After 8 weeks, rats treated with lithium alone showed marked impairment of renal concentrating ability and moderate degree of structural renal changes. Neuroleptics alone had no effect on concentrating ability or renal morphology, nor did they aggravate the changes caused by lithium. In fact, neuroleptics seemed to improve the concentrating ability in rats treated with lithium. It is concluded that in rats high doses of neuroleptics do not potentiate lithium-induced functional and structural renal changes.