Article date: July 1994
By: Michael J. Durcan, Philip F. Morgan, Michelle L. Etten, Markku Linnoila, in Volume 112, Issue 3, pages 855-860
Administration of the irreversible antagonist, N‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline, (EEDQ, 2 mg kg−1, i.p.) to mice reduced binding of [3H]‐RX 821002 (2‐methoxy‐idazoxan) to α2‐adrenoceptors in whole mouse brain by 75% 24 h later. The receptor binding returned over time only being reduced by 25% by 16 days post administration; the time taken for binding to return to 50% of control levels was estimated to be 5.25 days.
EEDQ administration also resulted in the loss of the sedative effect of the α2‐adrenoceptor agonist, medetomidine, measured by the holeboard test of directed exploration and locomotor activity. Agonistinduced sedation returned to control values by 8 days post EEDQ administration.
EEDQ administration also resulted in the loss of the hypothermic response to medetomidine (0.1 mg kg−1, i.p.). Medetomidine‐induced hypothermia returned to control values by 12 days post EEDQ administration.
Pretreatment with the selective α2‐adrenoceptor antagonist, RX 821002 (0.1–3.0 mg kg−1, i.p.) 45 min before EEDQ prevented the loss of α2‐adrenoceptors as well as the blockade of medetomide‐induced sedation and hypothermia by EEDQ.
The results of these experiments indicate that there is significant receptor reserve for α2‐adrenoceptor‐mediated behavioural and physiological responses.
Administration of the irreversible antagonist, N‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline, (EEDQ, 2 mg kg−1, i.p.) to mice reduced binding of [3H]‐RX 821002 (2‐methoxy‐idazoxan) to α2‐adrenoceptors in whole mouse brain by 75% 24 h later. The receptor binding returned over time only being reduced by 25% by 16 days post administration; the time taken for binding to return to 50% of control levels was estimated to be 5.25 days.
EEDQ administration also resulted in the loss of the sedative effect of the α2‐adrenoceptor agonist, medetomidine, measured by the holeboard test of directed exploration and locomotor activity. Agonistinduced sedation returned to control values by 8 days post EEDQ administration.
EEDQ administration also resulted in the loss of the hypothermic response to medetomidine (0.1 mg kg−1, i.p.). Medetomidine‐induced hypothermia returned to control values by 12 days post EEDQ administration.
Pretreatment with the selective α2‐adrenoceptor antagonist, RX 821002 (0.1–3.0 mg kg−1, i.p.) 45 min before EEDQ prevented the loss of α2‐adrenoceptors as well as the blockade of medetomide‐induced sedation and hypothermia by EEDQ.
The results of these experiments indicate that there is significant receptor reserve for α2‐adrenoceptor‐mediated behavioural and physiological responses.
DOI: 10.1111/j.1476-5381.1994.tb13158.x
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