Enhanced hypotensive response to intravenous apomorphine in chronic spinalized, conscious rats: role of spinal dopamine D(1) and D(2) receptors.
Intravenous (i.v.) treatment with apomorphine (0.3 mg/kg) in conscious rats with chronic spinal cord transection (at T5-T7) induced a significant hypotension, which was greater than that in sham-operated rats. The present study examined whether such an amplification results from an enhanced spinal dopamine D(1) and/or D(2) receptor-mediated depressor effect. Intrathecal (i.t.) pretreatment with domperidone (40 microg/rat at T9-T10), a dopamine D(2) receptor antagonist that does not cross the blood-brain barrier, blocked nearly 35 and 56% of the maximal apomorphine-induced hypotension in control and spinal rats, respectively. The remaining hypotension after i.v. domperidone (0.5 mg/kg) pretreatment (i.e. the spinal component of the response) was significantly greater in spinal rats than in controls. In the latter animals, apomorphine-induced hypotension was fully abolished by metoclopramide (5 mg/kg, i.v.). However, in spinal rats, the hypotension was only abolished by combined pretreatment with i.v. metoclopramide and i.t. SCH 23390 (27 microg/rat at T9-T10). The results suggest that the enhancing hypotensive effects of i.v. apomorphine by spinal cord section are related to increased spinal dopamine D(1) and D(2) receptor-mediated depressor effects.
Lahlou
Saad
S
Centro de Ciências Biológicas, Universidade Federal de Pernambuco, 50670-901 Recife, PE, Brazil. lahlou@npd.ufpe.br
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003243:Consciousness; D004294:Domperidone / Q000008:administration & dosage / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D007022:Hypotension / Q000139:chemically induced*; D007278:Injections, Spinal; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013904:Thoracic Vertebrae
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004294:Domperidone; D008787:Metoclopramide; D001058:Apomorphine