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

Abstract

Rats were given p‐chlorophenylalanine (PCPA, 150 mg kg−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, 150 mg kg−1, 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+. 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. 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. 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. 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. 1991 British Pharmacological Society