ACTION POTENTIAL-DEPENDENT OUTPUT OF 5-HYDROXYTRYPTAMINE IN THE ANESTHETIZED RAT AMYGDALOPIRIFORM CORTEX IS STRONGLY INHIBITED BY TONIC 5-HT1B-RECEPTOR STIMULATION

The output of 5-hydroxytryptamine (5-HT) from the amygdalopirifrom cor tex has been measured in anaesthetized rats using intracerebral microd ialysis 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 ant agonist metergoline through the dialysis probe resulted in a greater t han 10-fold increase in the overflow of 5-HT. The major portion of thi s increase occurred in the range 1-3 mu M metergoline, and was complet ely attenuated by inclusion of tetrodotoxin. More specific 5-HT antago nists, such as cyanopindolol, also enhanced output, but to a lesser ex tent. The pharmacological profile of the receptors mediating the effec t was similar to that of the 5-HT1B type, which are often found presyn aptically on 5-HT-containing nerve terminals. Other drugs were also ca pable of altering the output of 5-HT; in particular, muscimol reduced dialysate 5-HT content, while propranolol increased it. The 5-HT uptak e inhibitor citalopram significantly increased the overflow of 5-HT, b ut only by about 80% above basal levels. It is concluded that the rele ase of 5-HT from the rat amygdalopiriform cortex in vivo is tightly re stricted due to activation of 5-HT1B receptors. Small alterations in s uch activation, however, can lead to large changes in 5-HT output, sug gesting a possible mechanism by which neurotransmission through the am ygdalopiriform cortex may become unstably amplified. These results may be of significance to the generation of epileptic activity in the amy gdala or piriform cortex.