Two groups of normal male volunteers were administered oral haloperidol at two dose levels: 4 mg (n = 12), and 10 mg (n = 9). Subjects were administered the Symbol-Digit Substitution Test (SDST) prior to drug administration (0 hours) and at the following intervals after administration: 1, 3, 4, 6, 14, 24, and 36 hours. Overall performance of the 10-mg group was poorer than that of the 4-mg group. Both groups showed a significant time-dependent decrease in performance, with the effects for the 10-mg group being apparent earlier and lasting longer. The time course for this decrease corresponded to the time course of elevation of prolactin by haloperiodol in these subjects. Performance on the Flexibility of Closure Test was unimpaired in subjects receiving 10 mg haloperiodol, indicating that the impairment in performance on the SDST was not exclusively due to nonspecific factors such as sedation or psychomotor retardation. Extrapyramidal side effects could have contributed to impairment on the SDST, but the time course of these effects was different than that of performance impairment. Results indicate that haloperidol may have dose-dependent differential adverse effects on task performance when administered on a short-term basis, although little is known about the exact nature of these effects and their relationship to antipsychotic activity of the drug. Even though these effects may clear with repeated administration, their presence even for a short time may contribute adversely to the risk-benefit profile of neuroleptic medication. On a theoretical level, these results provide evidence that relatively specific dopamine antagonists may produce differential effects on psychometric task performance, the magnitude and time course of which correspond to dopamine antagonist mediation of prolactin release, and suggest an interaction between dopamine pathways and information-processing activities of the brain.
|Original language||English (US)|
|Number of pages||9|
|State||Published - Mar 1989|
- Tranquilizing agents, major
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