Anti-aversive role of serotonin in the dorsal periaqueductal grey matter.

Microinjection of 5, 10, and 20 nmol serotonin (5-HT) and of 0.5, 1, and 2 nmol 5-methoxy-N, N-dimethyltryptamine (5-MeODMT) into the dorsal midbrain of rats bearing chronically implanted chemitrodes raised the electrical threshold for inducing escape behaviour following stimulation of the dorsal periaqueductal grey matter (DPAG). Linear regressions of log dose against drug-induced increase in aversive threshold were obtained for 5-HT and 5-MeODMT. The 5-MeODMT dose-effect curve was steeper and lay to the left of the 5-HT dose-effect curve. Local pre-treatment with 10 nmol metergoline or ketanserin blocked the anti-aversive effect of 10 nmol 5-HT, whereas pre-treatment with 100 nmol zimelidine potentiated this effect of 5-HT. The same dose of zimelidine raised the aversive threshold when given alone. These results suggest that 5-HT plays an inhibitory role in the DPAG controlling aversion, probably mediated by 5-HT2 receptors.