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.
Robinson
E S
ES
Psychopharmacology Unit, School of Medical Sciences, University Walk, Bristol.
Nutt
D J
DJ
Jackson
H C
HC
Hudson
A L
AL
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D006120:Grooming / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
D016376:Oligonucleotides, Antisense; D018341:Receptors, Adrenergic, alpha-2