Episodic barrel rotations induced by intrastriatal injection of quinolinic acid in rats. Inhibition by anticonvulsants.
Unilateral intrastriatal injection of quinolinic acid (2,3 pyridine dicarboxylate; QUIN) in the rat produces episodic barrel rotations and tonic-clonic forepaw movements, lasting for several hours. We investigated whether intraperitoneal posttreatment with anticonvulsants could abolish this phenomenon when it is already fully developed, and whether their potency ratio was similar in models of epilepsy. All 8 tested antiepileptics, namely carbamazepine, clonazepam, diazepam, diphenylhydantoin, ethosuximide, flunarizine, phenobarbital and sodium valproate decreased this behaviour in a dose-dependent way. Six other drugs with anticonvulsant properties were also effective: DL-2-amino-7-phosphonoheptanoic acid, desipramine, etomidate, ketamine, meprobamate and sabeluzole. The ED50-values for halving the frequency of the episodes of barrel rotation correlated well with published ED50-values for inhibition of tonic hindpaw extension in the maximal metrazol seizure test (rs = .95, p less than 0.001) and with the ED50-values for halving the duration of the forepaw clonus in the rat-kindling model (rs = .93, p less than 0.001). This quinolinic acid test allows visualization of the onset of action of anticonvulsants, with each animal as its own control. In order to assess whether this test is also sensitive to drugs influencing the symptoms of Huntington's disease, the effect of the dopamine antagonists haloperidol and pimozide, the acetylcholinesterase inhibitor physostigmine and the anticholinergics atropine and dexetimide were investigated as well. The experiments suggested that the barrel rotations and clonic forepaw movements, only 3-6 hours after intrastriatal injection of QUIN respond to anticonvulsants, but are not specifically sensitive to drugs used in the symptomatic treatment of Huntington's disease.
Marrannes
R
R
Department of Neuropsychopharmacology, Janssen Research Foundation, Beerse, Belgium.
Wauquier
A
A
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum; D008297:Male; D009069:Movement Disorders / Q000139:chemically induced*; D011725:Pyridines / Q000494:pharmacology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012399:Rotation
D000927:Anticonvulsants; D011725:Pyridines; D011805:Quinolinic Acids; D017378:Quinolinic Acid