A novel in vivo test for drugs affecting central serotonergic and adrenergic systems.
In urethane-anaesthetized rats, myoclonic twitches of the anterior digastricus muscle were evoked by L-5-hydroxy-tryptophan (L-5-HTP, 50-100 mg/kg iv.), the serotonin (5-HT) receptor agonist, quipazine (1-8 mg/kg i.v.) and the 5-HT releaser, fenfluramine (4-8 mg/kg i.v.). The effect of L-5-HTP or quipazine on the frequency of twitches was inhibited by the 5-HT receptor antagonist cyproheptadine. Also L-DOPA (100 mg/kg i.p.) or the alpha 1-adrenoceptor agonist, cirazoline (0.3-3 mg/kg i.v.) evoked twitches of the muscle which were inhibited by the alpha 1-adrenoceptor antagonist, prazosin. In decerebrate, artificially respired rats, neither L-5-HTP nor L-DOPA evoked the twitches. The frequency of twitches evoked by fenfluramine but not by L-DOPA was increased by the alpha 2-adrenoceptor agonist, clonidine (0.2 and 0.4 mg/kg i.v.); clonidine's effect was abolished by the alpha 2-adrenoceptor antagonist, yohimbine. The beta 2-adrenoceptor agonist, salbutamol (0.01-1 mg/kg i.v.) had no effect on fenfluramine-induced twitches. It is concluded that (1) activation of 5-HT receptors or alpha 1-adrenoceptors in the brain of urethane-anaesthetized rats evokes twitches of the anterior digastricus muscle, and (2) this preparation can be utilized as a test to study the action of compounds on central 5-HT and adrenergic systems.
Rawlow
A
A
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
King
R G
RG
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D003655:Decerebrate State; D005277:Fenfluramine / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009334:Neck Muscles / Q000187:drug effects; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D005277:Fenfluramine; D012701:Serotonin; D007980:Levodopa; D011814:Quipazine; D006916:5-Hydroxytryptophan; D003000:Clonidine; D000420:Albuterol