Effect of p‐chlorophenylalanine on release of 5‐hydroxytryptamine from the rat frontal cortex in vivo

Abstract

1 Rats were given p-chlorophenylalanine (PCPA, 150mgkg-1, i.p.) to inhibit partially 5-hydroxytryptamine (5-HT) synthesis so that its concentration in the frontal cortex fell by about half. The effects of this treatment on frontal cortex dialysate 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined before and after stimulation by increasing K+ concentration in the perfusion fluid by 100 mm for 20 min. Rates of 5-HT synthesis as indicated by the effects of 3-hydroxybenzylhydrazine (NSD 1015, 150mg kg-, i.p.) on frontal cortex tissue and dialysate 5-hydroxytryptophan (5-HTP) and dialysate 5-HIAA were also measured in rats that had not been stimulated with K+. 2 Dialysate 5-HT and 5-HIAA concentrations of both vehicle-and PCPA-treated rats fell into major (group 1) and minor (group 2) populations statistically distinguishable from each other by the high 5-HT and low 5-HIAA values of the latter group. 3 In group 1 animals, PCPA decreased both the dialysate 5-HT concentration and its rise following stimulation by K+ in proportion with the decrease of 5-HT in frontal cortex tissue. 5-HIAA fell more markedly than 5-HT and in similar proportion in both tissue and dialysate. The fall of dialysate 5-HIAA on stimulation by K+ was also attenuated to the same degree. The elevated 5-HT/5-HIAA ratios after PCPA treatment imply increased conservation of the depleted 5-HT stores. 4 PCPA decreased the above 5-HIAA values and the effects of NSD 1015 on tissue 5-HTP or dialysate 5-HIAA concentrations in similar proportion. However, PCPA had little effect on corresponding dialysate 5-HTP values. 5 The results are discussed with respect to relationships between synthesis, storage and release of 5-HT. They indicate that (under the conditions of the present study) the availability of 5-HT to receptors is directly proportional to total vesicular stores under both basal conditions and during neuronal firing.

An approach for serotonin depletion in pigs: Effects on serotonin receptor binding

“…Our data from the pig brain are in line with similar studies in rats where pCPA is found to effectively and selectively decrease 5-HT and 5-HIAA tissue concentrations (Koe and Weissman, 1966;Kornum et al, 2006;O'Connell et al, 1991). The higher percentages of serotonin depletion (>90%) achieved in rats are likely to be explained by the higher doses of pCPA (250-400 mg/kg) and perhaps also by the route of administration (intraperitoneal vs. intramuscular) (Kornum et al, 2006;O'Leary et al, 2007;Paxinos et al, 1977), and furthermore, 100 mg/kg pCPA given to rats only resulted in 30% cortical serotonin depletion (Datla and Curzon, 1996).…”

Pathological Changes in Dopaminergic Nerve Cells of the Substantia Nigra and Olfactory Bulb in Mice Transgenic for Truncated Human α-Synuclein(1–120): Implications for Lewy Body Disorders

“…They were stored at Ϫ80°C for 2 d. On the day of analysis, the supernatants were thawed and mixed with 3,4-dihydroxybenzylamine as an internal standard. Levels of dopamine, homovanillic acid, and 5-hydroxytryptamine (5-HT) were determined by HPLC combined with electrochemical detection, as described previously (O'Connell et al, 1991).…”

Evidence for postsynaptic mediation of the hypothermic effect of 5‐HT1A receptor activation

“…As availability of 5-HT for release falls in proportion with its depletion by pCPA (O'Connell et al, 1991), a hypothermic effect of 5-HTIA agonists due to decreased release at axon terminals following activation of presynaptic receptors would be unlikely to survive the above pCPA treatments. Incidentally, Satinoff et al (1991) found that pCPA was acutely hypothermic but, in agreement with our findings, temperature was normal on the day after injection.…”