Behavioural and physiological effects induced by an infusion of antisense to α 2D ‐adrenoceptors in the rat

The aim of this study was to investigate the behavioural and physiological effects of an i.c.v. infusion of antisense oligonucleotide to the α 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. 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 α 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. 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. Pupil diameters of rats infused with antisense to α 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. In conclusion, an i.c.v. infusion of antisense to the α 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.British Journal of Pharmacology (2000) 130 , 153–159; doi: 10.1038/sj.bjp.0703296