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


CONCLUSIONS
The results confirm that alpha 2 antagonists delay-dependently impair choice accuracy in a delayed-response paradigm.
McAllister
K H
KH
Novartis Pharma, Nervous System Department, WSJ-106.241, 4002 Basel, Switzerland. kevin.mcallister@pharma.novartis.com
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019329:Idazoxan / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D012601:Scopolamine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018727:Muscarinic Antagonists; D015016:Yohimbine; D012601:Scopolamine; C058525:2-methoxyidazoxan; D019329:Idazoxan