HALOPERIDOL DOES NOT PRODUCE DOPAMINE CELL DEPOLARIZATION-BLOCK IN PARALYZED, UNANESTHETIZED RATS

A widely accepted theory postulates that chronic treatment with neurol eptics causes, in rats, the depolarization block of the majority of mi dbrain dopamine (DA) neurons. However, we reported that such treatment fails to reduce the number of spontaneously active DA neurons when th e neuronal sampling is performed in the D-tubocurarine-paralyzed inste ad of chloral-hydrate anesthetized preparation. The present experiment s were aimed at verifying whether the negative results might be due to the use of D-tubocurarine as paralyzing agent. Rats were chronically treated with haloperidol (0.5 mg kg(-1) i.p., daily) for 3 to 4 weeks. Two to three hours after the last injection, the number of spontaneou sly active DA neurons in the ventral tegmental area (VTA) were sampled , and their discharging characteristics analyzed, both in animals unde r chloral hydrate anesthesia and in rats immobilized either with D-tub ocurarine, gallamine or succinylcholine. The results indicate that chr onic treatment with haloperidol reduced the number of spontaneously ac tive VTA-DA neurons by about 65% in animals under chloral hydrate anes thesia, but failed to modify the number of spontaneously firing DA neu rons in rats immobilized with D-tubocurarine, gallamine or succinylcho line. The results indicate that the depolarization block of DA neurons does not occur in the paralyzed preparation and raise doubts about th e presence of this phenomenon in the intact non-anesthetized unrestrai ned animal. (C) 1998 Elsevier Science B.V.