High-dose clonidine motor syndrome: relationship to serotonin syndrome.
Reciprocal forepaw treading, hindlimb abduction, and Straub tail are some of the abnormal motor behaviors of the classical 'serotonin syndrome,' which results from activation of serotonin (5-HT) receptors. However, we also observed them in the syndrome evoked by the alpha-adrenergic agonist clonidine, at high doses (5-40 mg/kg). Other features of the clonidine syndrome (scored from videotapes) were body and head tremor, forelimb hyperextension, ataxia, vertical jumping, tactile hyperreactivity, and autonomic signs (piloerection, pupillary dilatation, salivation, proptosis). The clonidine syndrome persisted for several hours and was not lethal. Clonidine suppressed locomotor activity (photocell recording) and induced episodes of catalepsy and 5-HT-independent impairment of motor habituation. Single high doses of drugs active at several different neurotransmitter receptors significantly reduced total behavioral score through effects primarily on tremor and autonomic signs, but none prevented the clonidine syndrome. Lesions of monoaminergic neurons [intracisternal 5,7-dihydroxytryptamine (DHT) or 6-hydroxydopamine] or monoamine depletion by intraperitoneal reserpine all failed to prevent this motor syndrome. Co-administration of 5-HTP and clonidine did not exacerbate the clonidine syndrome in naive rats and did not prevent the onset of the serotonergic syndrome in rats with DHT lesions. These data suggest that neither catecholamines nor 5-HT have a major role in the serotonin-like behavioral responses to high doses of clonidine.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D054755:Imidazoline Receptors; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009069:Movement Disorders / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D013577:Syndrome; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D054755:Imidazoline Receptors; D011942:Receptors, Adrenergic, alpha; D018341:Receptors, Adrenergic, alpha-2; D011985:Receptors, Serotonin; D012701:Serotonin; D003000:Clonidine