A role for CNS alpha-2 adrenergic receptors in opiate-induced muscle rigidity in the rat.
A number of potential neurochemical mediators of opiate-induced muscle rigidity have been proposed based on the results of systemic drug studies and on knowledge of the brain sites implicated in opiate rigidity. The effects of i.c.v. pretreatment with selected opioidergic, alpha adrenergic and serotonergic drugs on muscle rigidity induced with systemic injection of the potent opiate agonist alfentanil (ALF) were investigated in spontaneously ventilating rats. The opiate antagonist methylnaloxonium (MN; 0.2-14 nmol), alpha-2 adrenergic agonists dexmedetomidine (DEX; 0.4-42 nmol) or 2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride (ST91; 4-400 nmol), alpha-1 adrenergic antagonist prazosin (PRZ; 7-70 nmol) or serotonergic antagonist ketanserin (KET; 18-550 nmol) were injected i.c.v. (10 microliters) and ALF (500 micrograms/kg s.c.) was administered 10 min later. S.c. electrodes were used to record gastrocnemius electromyographic activity. Both MN and DEX dose-dependently and potently antagonized ALF-induced rigidity. ST91 produced shorter-lived, less profound, antagonism of ALF rigidity. PRZ, at the highest dose tested, produced a delayed and modest reduction in ALF rigidity. A large, non-selective, dose of KET incompletely attenuated ALF rigidity. These results lend support to the hypothesis that central opioid and alpha-2 adrenergic receptors mediate opiate-induced muscle rigidity in the rat.
Weinger
M B
MB
Department of Anesthesiology, University of California at San Diego School of Medicine, La Jolla 92093.
Chen
D Y
DY
Lin
T
T
Lau
C
C
Koob
G F
GF
Smith
N T
NT
D000316:Adrenergic alpha-Agonists; D015760:Alfentanil / Q000494:pharmacology; D000818:Animals; D004576:Electromyography; D006614:Hindlimb; D007093:Imidazoles / Q000494:pharmacology; D007650:Ketanserin; D008297:Male; D020926:Medetomidine; D009127:Muscle Rigidity / Q000139:chemically induced* / Q000503:physiopathology*; D009270:Naloxone / Q000031:analogs & derivatives; D009294:Narcotics / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D009294:Narcotics; D000644:Quaternary Ammonium Compounds; D018341:Receptors, Adrenergic, alpha-2; D015760:Alfentanil; D009270:Naloxone; C041269:N-methylnaloxone; D007650:Ketanserin; D020926:Medetomidine