Do local vasomotor effects elicit the motor deficits induced by intrathecally applied substance P antagonists in the rat?
The intrathecal application of the substance P (SP) antagonists [D-Pro2,D-Trp7,9]SP (DPDT) and [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP (DAPTL) to the lumbar region of intact, freely moving rats produced laming of the hindlimbs at doses of 0.375 nmol and above, and 1.5 nmol and above, respectively. In addition, the administration of DPDT (doses of 25 and 0.18 nmol) and DAPTL (25 and 0.6 nmol) produced a powerful constriction of the dorsal median spinal vein (DMSV) in decerebrated, unanaesthetised rats. Intrathecal SP (25 or 1.0 nmol) had a similar action on the spinal circulation to DPDT and DAPTL, though laming was first observed at doses of 30 nmol and higher. This suggests that intrathecally applied SP antagonists do not elicit laming by causing an obstruction of the venous drainage of the spinal cord. Disturbances of the spinal circulation could, however, influence the results of behavioural or physiological experiments in which SP or its analogues are administered intrathecally.
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D007278:Injections, Spinal; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D010446:Peptide Fragments; D013373:Substance P; C045505:substance P (4-11), Pro(4)-Trp(7,9)-; C038073:substance P, Arg(1)-Pro(2)-Trp(7),(9)-LeuNH(2)(11)-