Biphasic effects of some dopamine agonists on striatal acetylcholine concentrations

Since the reduction of striatal dopaminergic transmission decreases striatal acetylcholine (ACh) levels due to disinhibition of the respective neurons, such an effect might be expected after selective stimulation of dopamine (DA) autoreceptors. The effects of a number of DA agonists, including the purportedly selective presynaptic agents 3-PPP and TL 99, on striatal ACh levels were investigated over a wide dose range. Apomorphine and 3-PPP decreased ACh levels in a lower dose range (0.01-0.03 mg/kg s.c. and 0.2-1 mg/kg s.c., resp.) TL 99 showed a significant, but much smaller effect (0.1-0.3 mg/kg s.c.), whereas piribedil and bromocriptine only increased ACh. However, 3-PPP (at 3 mg/kg and above) and TL 99 (at 3 mg/kg) increased ACh in much the same way as did conventional DA agonists. These results suggest (a) that pre- and postsynaptic DA receptors are distinct in a functionally relevant manner, and (b) that 3-PPP and TL 99 possess postsynaptic effects on DA receptors associated with cholinergic neurons. Since 3-PPP does not elicit stereo sterotypes in spite of evidence for an involvement of cholinergic neurons in the mediation of this behaviour it might be assumed that it acts on other postsynaptic DA receptors than does apomorphine. Moreover, it seems possible that the two types of DA receptors are located on two different types of cholinergic neurons with different functions.