Spinalization unmasks clonidine's alpha 1-adrenergic mediated excitation of the flexor reflex in rats.
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.
Kehne
J H
JH
Gallager
D W
DW
Davis
M
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D009407:Nerve Block; D010109:Oxymetazoline / Q000494:pharmacology; D011343:Procaine; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000601:surgery
D000316:Adrenergic alpha-Agonists; D011343:Procaine; D010109:Oxymetazoline; D003000:Clonidine