Central monoamine synapses as sites of action for ergot drugs

The acute and subacute effects of ergot drugs on central monoaminergic mechanisms were studied in the rat. The most significant findings are: 1. After acute treatment, lergotrile and bromocriptine were found to block apomorphine-induced locomotion and rearing, suggesting that these two ergot drugs can block postsynaptic DA receptors within the nucleus accumbens. 2. Several ergot drugs were shown to have high affinity for some 3H-ADTN binding sites. Earlier studies indicate that 3H-ADTN appears to label postsynaptic dopamine receptors located on nerve cells in the striatum. These ergot-sensitive 3H-ADTN binding sites appear not to be linked to the adenylate cyclase system. In addition, bromocriptine, unlike CM 29-712, was found to have a high affinity for 3H-spiperone binding sites in the striatum. 3. Bromocriptine and CM 29-712 increased norepinephrine turnover in periventricular and paraventricular hypothalamic areas, suggesting a blockade of norepinephrine receptors. CM 29-712 also increased DA turnover in the medial palisade zone of the median eminence. 4. Some ergot drugs also had affinity for 5-HT receptor binding sites, possibly reflecting a 5-HT agonistic action in some areas, as shown in behavioral studies. 5. Apomorphine and bromocriptine displaced in vivo 3H-spiperone binding in the hypothalamus, septal area, and substantia nigra, but not in the striatum. 6. Subacute treatment with bromocriptin and CM 29-712 were found to produce two types of changes in behavior: The apomorphine-induced locomotion was enhanced while the chewing and licking activity (stereotypies) was reduced. These behavioral changes may be associated with an increased affinity in the 3H-ADTN binding sites in the striatum. This treatment also produced persistent increases of DA turnover in the tuberculum olfactorium but not in striatum.