Effect of prolonged treatment with haloperidol on "emotional" defecation and movement in rats in a well-habituated environment.
Sixteen adult male Wistar rats were administered either haloperidol (n = 8), 0.5 mg/kg, or saline (placebo) (n = 8) by subcutaneous injection three times per week for 6 weeks, and were again injected after a 6-week drug-free period. The study was conducted in a well-habituated, distinctive environment to which the rats were introduced 1 hour before the injection on each occasion. The fecal bolus counts 1 hour before and 2 hours after drug injection were obtained, as well as movement counts repeatedly in epochs of 90 seconds upon introduction to the cages and after the injections. Haloperidol produced an overall increase in defecation in the 2 hours after drug injection compared with placebo. The post-drug bolus counts for haloperidol-treated rats were lower in week 2 compared with week 1, but the difference from placebo for this reduction was not significant, and it did not persist beyond week 4. The haloperidol-treated group showed a significant increase in the predrug bolus counts from week 5, suggesting a conditioned response to the cage environment. The haloperidol-treated rats were markedly less mobile than the placebo-treated rats, and with repeated exposure to haloperidol, they tended to develop hypomotility earlier. No tolerance to the movement effect was observed. The defecation and movement effects of haloperidol at 12 weeks were no different from those at week 1. This study supports earlier work indicating that haloperidol produces a dysphoric effect in rats, and it suggests that this effect does not habituate over 6 weeks of repeated administration. It does not replicate the motor aspect of akathisia seen in humans.
Sachdev
P
P
University of New South Wales, Australia.
Loneragan
C
C
Westbrook
F
F
D017109:Akathisia, Drug-Induced / Q000503:physiopathology; D000818:Animals; D003672:Defecation / Q000187:drug effects*; D004644:Emotions / Q000187:drug effects*; D006185:Habituation, Psychophysiologic / Q000502:physiology*; D006220:Haloperidol / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D006220:Haloperidol