The subtypes of presynaptic nicotinic acetylcholine receptors (nAChRs) that modulate dopamine (DA) release in the striatum have been well defined [1]. Evidence from pharmacological tools coupled with immunoprecipitation and transgenic mice indicate diverse nAChR containing α4, α5, α6, β2 and/or β3 subunits on DAergic terminals. There is also evidence for an indirect contribution from α7 nAChR, in slice preparations [2]. The local nicotinic modulation of DA release in the PFC has been less well studied. Here, the aim is to characterise the nAChR subtypes mediating DA release in rat PFC slices, for comparison with striatum. Chopped prisms (150μm) of striatum or PFC were loaded with 50nM [³H]DA and release assayed by filtration [2,3].The tissue was distributed onto a 96 well filter plate and incubated with buffer alone or plus antagonist (mecamylamine, 30μM; dihydrobetaerythrodine (DHβE), 10μM; α-conotoxin MII (αCnTxMII), 120nM; or α-bungarotxin (αBgt), 40nM) for 5 min. Buffer with or without antagonist was replaced with buffer containing agonists ((-)nicotine, 0.01-100μM; choline, 1-10mM; 5-IA85380, 0.001-1μM; PNU120596, 10μM). After 5min incubation, stimulated release was collected and samples counted for radioactivity. [³H]DA remaining in the tissue was also estimated to determine fractional DA release. Nicotine evoked concentration-dependent [³H]DA release from striatal slices (EC50 177 ± 10nM); this was abolished by mecamylamine, a broad spectrum nAChR antagonist. Similar responses were observed for the PFC slices but the maximum response was 75% of that from striatum. The β2* selective agonist 5-IA85380 evoked concentration-dependent [³H]DA release from both tissues and this was inhibited by the selective β2* nAChR antagonist DHβE. The α6* component of DA release was dissected using αCnTxMII, previously shown to inhibit responses by α6* nAChRs [4]. In contrast to striatum, immunoprecipitation experiments confirm that the α6 subunit does not contribute to nAChRs in the PFC. The α7 nAChR agonist choline evoked [³H]DA release from striatum and this was amplified by addition of the α7 positive modulator PNU120596 and abolished by αBgt. This drug combination revealed a contribution of pre-synaptic α7 nAChR to [³H]DA release in the PFC. This analysis is consistent with differences in the nAChR subunit composition of mesocorticolimbic versus nigrostriatal projections to PFC & striatum, respectively.