Effects of dopamine antagonists on alfentanil-induced locomotor activity in horses

To determine whether specific dopamine receptor antagonists block alfentanil-induced locomotor stimulation in horses.

Randomized, prospective, crossover experiment.

Eight adult horses (462-604 kg).

Doses of dopamine-1 (D1) (NNC 01-0756) and dopamine-2 (D2) antagonists (eticlopride) were selected in a pilot study prior to a three part, blinded, cross-over study. In part 1, horses received 7.5 micro g kg-1 eticlopride, 5 micro g kg-1 NNC 01-0756 or an equal volume of saline. In part 2, they received both antagonists and in part 3, acepromazine at 0.05 mg kg-1. Locomotor activity was assessed by counting the steps taken by a marked forefoot per 2 minutes. The D antagonist was injected IV after a 20-minute control period. The horses were observed for 10 minutes before alfentanil (20 micro g kg-1) was injected IV. Locomotor activity was then monitored for 60 minutes. Statistical analysis was performed on step counts following alfentanil normalised by subtracting the mean control step count from each value recorded after alfentanil. Data were analysed using Friedman tests and Tukey-Kramer comparisons.

Alfentanil increased locomotor activity for 10 minutes. NNC 01-0756 tended to reduce locomotor activity between 0 and 10 minutes (p = 0.261), but neither D antagonist suppressed it significantly. The combination of D antagonists induced more step counts than saline or acepromazine (p = 0.0265) in the 20-40-minute period and more than saline, acepromazine or eticlopride between 40 and 60 minutes (p = 0.0003).

Neither D1 nor D2 antagonists inhibited alfentanil-induced locomotor activity. Both drugs appeared to cause locomotor stimulation of their own.

D1 and D2 antagonism did not reduce opioid-induced excitement in horses and is not suitable for reducing the incidence of this unwanted side-effect of opioids.