Behavioural and physiological effects induced by an infusion of antisense to alpha(2D)-adrenoceptors in the rat.

1. The aim of this study was to investigate the behavioural and physiological effects of an i.c.v. infusion of antisense oligonucleotide to the alpha(2D)-adrenoceptor subtype. Behavioural and physiological parameters were monitored for 2 days before the infusion, throughout the 3-day infusion period and for 3 days following the end of the infusion. 2. The antisense infusion resulted in a significant increase in behavioural activity characterized by increased locomotion and grooming scores. Behavioural activity scores of rats treated with antisense to alpha(2D)-adrenoceptors were significantly higher than those of rats treated with vehicle (H(2)O) or the mismatch toxicity control on day 4 and day 5 and, significantly higher than vehicle controls on day 6. 3. Body weight gain was significantly reduced in the antisense-treated rats at the end of the study compared to the vehicle (34%) and mismatch groups (30%), although daily food and water intakes were not significantly different at any time point. 4. Pupil diameters of rats infused with antisense to alpha(2D)-adrenoceptors were significantly greater than those of animals treated either with vehicle or mismatch oligonucleotide on day 5 of the study. On day 6, the pupil diameters of these animals were still significantly greater than the mismatch group. 5. In conclusion, an i.c.v. infusion of antisense to the alpha(2D)-adrenoceptor induced behavioural activation in rats, increased pupil diameter and reduced total weight gain. These effects were specific to the antisense-treated group and were fully reversed post-infusion.