1. 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 alpha 2-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. 2.
EEDQ administration also resulted in the loss of the
sedative effect of the alpha 2-adrenoceptor agonist,
medetomidine, measured by the holeboard test of directed exploration and locomotor activity. Agonist-induced sedation returned to control values by 8 days post
EEDQ administration. 3.
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. 4. Pretreatment with the selective alpha 2-adrenoceptor antagonist,
RX 821002 (0.1-3.0 mg kg-1, i.p.) 45 min before
EEDQ prevented the loss of alpha 2-adrenoceptors as well as the blockade of medetomide-induced sedation and
hypothermia by
EEDQ. 5. The results of these experiments indicate that there is significant receptor reserve for alpha 2-adrenoceptor-mediated behavioural and physiological responses.