The alpha(2) adrenoceptor antagonists RX 821002 and yohimbine delay-dependently impair choice accuracy in a delayed non-matching-to-position task in rats

Rationale: alpha (2) adrenoceptor mechanisms appear to play a role in the p erformance of delayed response working memory tasks but there are contradic tory results. Objective: To investigate whether RX 821002 (2-methoxy-idazox an) and yohimbine and would affect the performance of the delayed non-match ing-to-position (DNMTP) task in rats and compare the effects to those of th e cholinergic antagonist scopolamine. Methods: Male Lister Hooded rats trai ned to criterion in an operant DNMTP task (0-48 s delay intervals) were adm inistered vehicle, RX 821002 (0.3, 1, 3 mg/kg s.c.), yohimbine (1, 3 mg/kg. s.c.) or scopolamine (0.05 mg/kg, s.c.). Together with choice accuracy, th e motor performance of the task was measured. Results: It was found that: ( 1) both RX 821002 and yohimbine statistically significantly reduced choice accuracy dose- and delay-dependently and in a similar magnitude to that of scopolamine while modifying the motor aspects of task performance delay-ind ependently and (2) RX 821002 produced mainly rate-decreasing effects. Yohim bine exerted stimulatory effects at the lowest dose and rate-decreasing eff ects at the highest dose, a profile consistent with that already described in operant tasks. Conclusion: The results confirm that alpha (2) antagonist s delay-dependently impair choice accuracy in a delayed-response paradigm.