Pre-synaptic nicotinic and D receptors functionally interact on dopaminergic nerve endings of rat and mouse nucleus...

The existence of pre-synaptic auto- and hetero receptors which modulate neurotransmitter release is well documented. Emerging evidence show that in some cases these pre-synaptic receptors may also cross-talk with each other. The aim of the present work was to investigate whether acetylcholine receptors (nAChRs) and dopamine (DA) autoreceptors, which are both able to modulate DA release, functionally interact on the same nerve endings. We used rat and mouse nucleus accumbens synaptosomes pre-labeled with [(3)H]DA and exposed to nicotinic and dopaminergic receptor ligands. Both nicotinic agonists and 4-aminopyridine (4-AP) provoked [(3)H]DA release which was inhibited by quinpirole and blocked by sulpiride and raclopride. Both the inhibitory effect of quinpirole and the stimulatory effect of (-)nicotine did not change when the nAChRs or the DA receptors were desensitized. (-)Nicotine and 4-AP were able to stimulate [(3)H]DA overflow also in mouse synaptosomes and this overflow was partially inhibited by quinpirole. In the beta(2) knockout mice quinpirole was still able to inhibit the [(3)H]DA overflow elicited by 4-AP. To conclude: in rat and mouse the (-)nicotine evoked-release can be modulated by D(2)/D(3) autoreceptors present on the DA terminals and nAChRs function is independent from D(2)/D(3) autoreceptors which themselves may function independently from the activation of nAChRs.