Altered responsiveness to substance P and 5-hydroxytryptamine in cat dorsal horn neurons after 5-HT depletion with p-chlorophenylalanine.
The responsiveness of functionally identified cat spinal dorsal horn neurons to iontophoretically applied substance P (SP) and 5-hydroxytryptamine (5-HT) has been investigated by means of extracellular recording after 5-HT depletion with p-chlorophenylalanine (p-CPA). In addition, the spinal levels of 5-HT, SP, cholecystokinin octapeptide, neurotensin, and vasoactive intestinal polypeptide have been measured in intact and p-CPA-pretreated cats. In the present study we have demonstrated an altered responsiveness of dorsal horn neurons to locally applied SP and 5-HT. We found in p-CPA-pretreated cats that the proportion of neurons responding with excitation to SP and 5-HT was significantly increased. At the same time, depression induced by 5-HT in the dorsal horn cells was virtually absent in p-CPA-pretreated animals. Our finding that spinal level of 5-HT was significantly decreased in p-CPA-treated animals is consistent with previous studies. No convincing alteration in the spinal levels of 4 analyzed peptides was found in p-CPA-treated animals. The present study has shown that pharmacological depletion of 5-HT has two major effects: (1) it increases significantly the proportion of dorsal horn neurons excited by SP and 5-HT; and (2) it is ineffective in inducing 5-HT supersensitivity. Further work is needed to explain mechanisms involved in these effects.
S
S
Jeftinija
C
C
Raspantini
M
M
Randić
T L
TL
Yaksh
V L
VL
Go
A A
AA
Larson
D000818:Animals; D002415:Cats; D005260:Female; D010134:Fenclonine / Q000494:pharmacology*; D007478:Iontophoresis; D008297:Male; D010455:Peptides / Q000032:analysis; D011903:Raphe Nuclei / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology* / Q000502:physiology; D013116:Spinal Cord / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D009435:Synaptic Transmission
D010455:Peptides; D012701:Serotonin; D013373:Substance P; D010134:Fenclonine