Pre-synaptic nicotinic and D2 receptors functionally interact on dopaminergic nerve endings of rat and mouse nucleus accumbens

We investigated whether nAChRs and D2 receptors co-exist and interact on the same nerve endings using synaptosomes prelabeled with [3H]DA and exposed to nicotinic anddopaminergic receptor ligands. The nicotinic agonists (-)nicotine or epibatidine provoked [3H]DA release which was inhibited by quinpirole. This effect was blocked by sulpiride and raclopride. The [3H]DA overflow evoked by 4-aminopyridine (4-AP) was markedly inhibited by quinpirole. This inhibitory effect did not change either in absence or in presence of (-)nicotine when the nAChRs were desensitized. The inhibitory effect of quinpirole disappeared after a preincubation with this drug. However, the stimulatory effect of (-)nicotine did not change when the D2 receptors were desensitized. (-)Nicotine and 4-AP were able to stimulate [3H]DA overflow also in mouse synaptosomes and this overflow was strongly inhibited by quinpirole. In the nAChR subunits β2 knockout mice the (-)nicotineevoked [3H]DA overflow did not occur anymore but quinpirole was still able to inhibit the [3H]DA overflow elicited by 4-AP. To conclude: in rat and mouse the (-)nicotine evokedrelease can be modulated by D2 autoreceptors coexisting in the same DA terminals and nAChRs function is independent from the activation of D2 autoreceptors which themselves may function independently from the activation of presynaptic nAChRs.