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The alpha 2 adrenoceptor antagonists RX 821002 and yohimbine delay-dependently impair choice accuracy in a delayed
1Novartis Pharma, Nervous System Department, WSJ-106.241, 4002 Basel, Switzerland. kevin.mcallister@pharma.novartis.com
Rationale:
alpha 2 adrenoceptor mechanisms appear to play a role in the performance of delayed response working memory tasks but there are contradictory results.
Objective:
To investigate whether RX 821002 (2-methoxy-idazoxan) and yohimbine and would affect the performance of the delayed non-matching-to-position (DNMTP) task in rats and compare the effects to those of the cholinergic antagonist scopolamine.
Methods:
Male Lister Hooded rats trained to criterion in an operant DNMTP task (0-48 s delay intervals) were administered 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, the 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-independently and (2) RX 821002 produced mainly rate-decreasing effects. Yohimbine exerted stimulatory effects at the lowest dose and rate-decreasing effects at the highest dose, a profile consistent with that already described in operant tasks.
Conclusion:
The results confirm that alpha 2 antagonists delay-dependently impair choice accuracy in a delayed-response paradigm.