Altered responsiveness to substance P and 5-hydroxytryptamine in cat dorsal horn neurons after 5-HT depletion with p-chlorophenylalanine

Jeftinija, Srdija; Raspantini, C.; Randić, Mirjana; Yaksh, Tony L.; Go, Vay Liang W.; Larson, Alice A.

doi:10.1016/0006-8993(86)91047-4

Cited by 13 publications

(1 citation statement)

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“…On the other hand, coexistence has been most extensively investigated in the rat medullary raphe nuclei projecting to the spinal cord, where substance P (SP) and thyrotropin-releasing hormone (TRH) immunoreactivity have been detected in 5-HT-containing soma (for review, see Hokfelt et al, 1987). Prior treatment of cats with PCPA has been shown to enhance markedly the excitatory effect of the microiontophoretic application of SP and as well as that of 5-HT onto dorsal horn neurons, without altering SP content of the spinal cord (Jeftinija et al, 1986). In the rat, an increase in SP content of the midbrain raphe nuclei has been reported following short-term PCPA administration (Savard et al, 1984), although in these latter regions SP immunostaining may reflect terminal projections of SP-containing neurons originating from outside the raphe (Hokfelt et al, 1987;Neckers et al, 1979).…”

Section: 7-dhtmentioning

confidence: 99%

Effect of short‐term serotonin depletion on the efficacy of serotonin neurotransmission: Electrophysiological Studies in the Rat central Nervous System

Chaput¹,

Lesieur²,

Montigny³

1990

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The effects of short-term serotonin (5-HT) depletion by p-chlorophenylalanine (PCPA) on the firing activity of dorsal raphe nucleus 5-HT neurons, on the responsiveness of dorsal hippocampus pyramidal neurons to microiontophoretically applied 5-HT and on the efficacy of the electrical stimulation of the ascending 5-HT pathway in suppressing the firing activity of CA3 dorsal hippocampus pyramidal neurons were assessed in chloral hydrate-anesthetized rats. PCPA (250 mg/kg/day i.p. for 2 days) reduced the 5-HT content of the dorsal hippocampus by 90%. However, the number of spontaneously active 5-HT neurons per microelectrode trajectory through the dorsal raphe or their average rate of firing was unaltered. The effect of afferent 5-HT pathway stimulation was reduced in only 40% of treated rats, whereas the sensitivity of CA3 pyramidal neurons to microiontophoretic 5-HT was not modified. The function of the terminal 5-HT autoreceptor was assessed using methiothepin, an autoreceptor antagonist. Methiothepin (1 mg/kg, i.v.) significantly enhanced the efficacy of the stimulation in PCPA-treated rats, although the degree of enhancement was much less than in controls. A greater reduction of the effectiveness of the stimulation was obtained by increasing the dose of PCPA (350 mg/kg/day i.p. for 2 days). This regimen reduced the 5-HT content of the dorsal hippocampus by 95%. In these rats, the sensitivity of the terminal 5-HT autoreceptor was assessed by increasing the frequency of the stimulation from 1 to 5 Hz. This procedure reduced to a similar extent the efficacy of the stimulation in treated and control rats, suggesting that the reduced effectiveness of methiothepin in enhancing 5-HT synaptic transmission in PCPA-treated rats is due to a lower degree of activation of the terminal 5-HT autoreceptor. The present results showing that the 350 mg/kg/day regimen of PCPA, but not the 250 mg/kg/day regimen, reduced the efficacy of the stimulation of the ascending 5-HT pathway suggest that a greater than 90% depletion is required to affect 5-HT neurotransmission significantly. The reduced level of activation of terminal 5-HT autoreceptors in rats treated with the lower dose of PCPA may facilitate the release of the remaining 5-HT per stimulation-triggered action potential, ensuring a virtually unaltered synaptic efficacy.

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Section: 7-dhtmentioning

confidence: 99%