Dissociation of the alpha 2-adrenergic antinociception from sedation following microinjection of medetomidine into the locus coeruleus in rats.
It is well established that alpha 2-adrenoceptor agonists have sedative and antinociceptive properties. In the current behavioral study we tried to find out if the alpha 2-adrenergic sedative and antinociceptive effects can be dissociated. We tested the hypothesis that alpha 2-adrenergic sedation is mediated by the locus coeruleus (LC) and antinociception by spinal alpha 2-adrenoceptors. Also, we addressed the possibility that intracerebral injection of an alpha 2-agonist might produce its antinociceptive effect by an action directly at the spinal cord. Medetomidine, an alpha 2-adrenergic agonist, or atipamezole, an alpha 2-adrenergic antagonist, were microinjected bilaterally into the LC through chronic cannulae in unanesthetized Han-Wistar rats. The effect on locomotor activity (/vigilance), tail-flick and hot-plate response, and on formalin-induced pain behavior was determined. Medetomidine microinjected into the LC (1-10 micrograms/cannula) produced dose-dependently hypolocomotion (/sedation), increase of response latencies in the hot-plate and the tail-flick tests, and a decrease in the formalin-induced pain behavior. Hypolocomotion (/sedation) was obtained at a lower medetomidine dose (1 microgram/cannula) than antinociception (3-10 micrograms/cannula). The lowest medetomidine dose used (1 microgram/cannula), which induced significant hypolocomotion (/sedation), produced either no antinociception (hot-plate and tail-flick tests) or even a slight hyperalgesia (formalin test). The hypolocomotion (/sedation) but not antinociception (tail-flick test) induced by systemic administration of medetomidine (100 micrograms/kg s.c.) could be reversed by atipamezole (10 micrograms/cannula) microinjected into the LC. Only a high systemic dose of atipamezole (1 mg/kg s.c.) reversed the antinociceptive effects of medetomidine.(ABSTRACT TRUNCATED AT 250 WORDS)
Pertovaara
Antti
A
Department of Physiology, University of Helsinki, HelsinkiFinland.
Hämäläinen
Minna M
MM
Kauppila
Timo
T
Mecke
Ernst
E
Carlson
Synnöve
S
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003655:Decerebrate State; D005557:Formaldehyde; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D020926:Medetomidine; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D006993:Hypnotics and Sedatives; D007093:Imidazoles; C050701:atipamezole; D005557:Formaldehyde; D020926:Medetomidine