Action potential-dependent output of 5-hydroxytryptamine in the anaesthetized rat amygdalopiriform cortex is strongly inhibited by tonic 5-HT1B-receptor stimulation.

The output of 5-hydroxytryptamine (5-HT) from the amygdalopirifrom cortex has been measured in anaesthetized rats using intracerebral microdialysis followed by HPLC analysis. Basal output overall of 5-HT was 2.558 +/- 0.351 fmol/20 min sampling period. Application of the 5-HT antagonist metergoline through the dialysis probe resulted in a greater than 10-fold increase in the overflow of 5-HT. The major portion of this increase occurred in the range 1-3 microM metergoline, and was completely attenuated by inclusion of tetrodotoxin. More specific 5-HT antagonists, such as cyanopindolol, also enhanced output, but to a lesser extent. The pharmacological profile of the receptors mediating the effect was similar to that of the 5-HT1B type, which are often found presynaptically on 5-HT-containing nerve terminals. Other drugs were also capable of altering the output of 5-HT; in particular, muscimol reduced dialysate 5-HT content, while propranolol increased it. The 5-HT uptake inhibitor citalopram significantly increased the overflow of 5-HT, but only by about 80% above basal levels. It is concluded that the release of 5-HT from the rat amygdalopiriform cortex in vivo is tightly restricted due to activation of 5-HT1B receptors. Small alterations in such activation, however, can lead to large changes in 5-HT output, suggesting a possible mechanism by which neurotransmission through the amygdalopiriform cortex may become unstably amplified. These results may be of significance to the generation of epileptic activity in the amygdala or piriform cortex.