Pharmacological characteristics of tremor, rigidity and hypokinesia induced by reserpine in rat.
The experiments characterized the dose- and time-dependence of parkinsonian motor signs induced by reserpine in rats and a standardized system of manipulation of animals, evaluation of symptoms and analysis of data was devised. The assay procedure yielded no more than 0.5, 4.5 and 0.0% false positives with the evaluation of tremor, rigidity and hypokinesia, respectively. A dose-dependent and often complete blockade of all three signs was obtained with L-DOPA plus carbidopa (10:1) as well as with other classes of pharmacological agents that are used in the treatment of Parkinson's disease, i.e. direct or indirect dopamine (DA) agonists (amantadine, pergolide, lisuride) and inhibitors of monoamine oxidase (MAO) (clorgyline, pargyline, deprenyl, tranylcypromine). The inhibitor of the uptake of DA, nomifensine, and anticholinergics, 5-hydroxytryptamine (5-HT) antagonists, histamine antagonists and tricyclic antidepressants exerted little or no effect. The effects of putative agonists and antagonists at alpha 1- and alpha 2-adrenoceptors were also examined. Yohimbine blocked tremor and rigidity, but not hypokinesia, at 0.66 and 0.28 mg/kg, respectively. It is suggested that alpha-adrenergic mechanisms and, in particular, alpha 2-adrenoceptors, may be involved in reserpine-induced tremor and rigidity. Noradrenergic and dopaminergic systems can conceivably interact to progressively generate these different motor signs.
Colpaert
F C
FC
Department of Psychopharmacology, Janssen Pharmaceutica, Beerse, Belgium.
D000818:Animals; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009069:Movement Disorders / Q000139:chemically induced*; D009127:Muscle Rigidity / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology; D012110:Reserpine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013550:Swimming; D013565:Sympatholytics / Q000494:pharmacology; D013997:Time Factors; D014202:Tremor / Q000139:chemically induced*
D008996:Monoamine Oxidase Inhibitors; D011941:Receptors, Adrenergic; D013565:Sympatholytics; D007980:Levodopa; D012110:Reserpine; D006220:Haloperidol; D004298:Dopamine