Figure 1.
Nicotinic (nAChRs) and muscarinic (mAChRs) receptors modify frequency-dependence of dopamine release. (A,B) Profiles of mean extracellular concentration of dopamine [DA]o ± SEM versus time in NAc after stimuli (arrows) of either a single pulse (1p) or a high frequency burst (4p/100 Hz) in control or drug conditions (DHβE, 1 μM; Oxo-M, 10 μM). Data are normalized to peak [DA]o released by 1p in controls. Either β2*-nAChR antagonist (DHβE) or mAChR agonist (Oxo-M) reduce release by a single pulse and enhance release by a burst thereby increasing the contrast between dopamine released by burst and non-burst activity. (C,D) Mean peak [DA]o ± SEM versus frequency during four pulse trains (1–100 Hz) in control (filled circles) or DHβE (squares) or Oxo-M (triangles) normalized to [DA]o released by a single pulse in control conditions. Either blockade of nAChRs with DHβE, or activation of mAChRs with Oxo-M results in increased frequency-dependence of dopamine release as described previously (see Rice and Cragg, 2004; Exley et al., 2008; Threlfell et al., 2010). (E) Schematic illustrating the frequency-dependence of dopamine release during deactivation of nAChRs as a result of either blockade/desensitization of presynaptic nAChRs on dopamine terminals or activation of mAChRs on cholinergic interneurons.