Journal of Neuroscience, Vol 5, 1583-1590, Copyright © 1985 by Society for Neuroscience
Spinalization unmasks clonidine's alpha 1-adrenergic mediated excitation of the flexor reflex in rats
JH Kehne, DW Gallager and M Davis
Clonidine exerts alpha 2-adrenergic mediated depressant effects on most
behaviors measured in a normal animal. However, in the spinal- transected
(spinalized) animal, clonidine apparently facilitates the flexor reflex
through a stimulation of spinal alpha 1-adrenoceptors. The purpose of the
present study was to determine if spinalization per se causes the shift in
clonidine's profile from an alpha 2- to an alpha 1-adrenergic agonist. The
hindlimb flexor reflex was elicited by electrical pulses delivered through
electrodes implanted subcutaneously in the hindpaw and was measured with a
force transducer and polygraph. In contrast to an alpha 2-adrenergic
mediated inhibition of the flexor reflex in intact rats, clonidine produced
an alpha 1-adrenergic mediated increase in flexor reflex amplitude in
spinalized rats. Because decerebration did not alter the depression due to
clonidine, and intraventricular (but not intrathecal) administration of
oxymetazoline mimicked the effect of clonidine, the depressant effects of
alpha 2-adrenergic agonists are mediated through alpha 2-adrenergic
receptors localized in the brainstem. Alternate methods for inducing a
functional spinal transection (spinal block with intrathecal procaine;
spinal ligation) indicated that the shift in clonidine's effect from
inhibition of the flexor reflex to excitation occurred immediately
following spinalization. Spinal ligation did not produce alpha 1-
adrenergic supersensitivity at 15 min or 2 hr after transection, as
measured by alterations in [3H]prazosin receptor binding or behavioral
responses to clonidine. Thus, the shift in clonidine's effects from alpha
2-adrenergic mediated inhibition of the flexor reflex in intact rats to
alpha 1-adrenergic mediated excitation in spinalized rats results because
spinal transection unmasks clonidine's alpha 1- adrenergic stimulatory
effect. Other conditions under which clonidine exerts alpha 1-adrenoceptor
mediated excitatory effects on behavior are discussed.