Nicotine smoking concentrations modulate GABAergic synaptic transmission in murine medial prefrontal cortex by activation of α7*and β2*nicotinic receptors

Nicotine is the major addictive component of cigarettes, reaching a brain concentration of similar to 300 nM during smoking of a single cigarette. The prefrontal cortex (PFC) mechanisms underlying temporary changes of working memory during smoking are incompletely understood. Here, we investigated whether 300 nM nicotine modulates gamma-aminobutyric acid (GABA) ergic synaptic transmission from pyramidal neurons of the output layer (V) of the murine medial PFC. We used patch clamp in vitro recording from C57BL/6 mice in the whole-cell configuration to investigate the effect of nicotine on pharmacologically isolated GABAergic postsynaptic currents (IPSCs) in the absence or presence of methyllycaconitine (MLA) or dihydro-beta-erythroidine (DH beta E), selective antagonists of alpha 7- and beta 2-containing (alpha 7* and beta 2*) nicotinic acetylcholine receptors (AChRs), respectively. Our results indicated that nicotine, alone or in the presence of MLA, decreases electrically evoked IPSC (eIPSC) amplitude, whereas in the presence of DH beta E, nicotine elicited either an eIPSCs amplitude increase or a decrease. In the presence of DH beta E, nicotine increased membrane conductance leaving the paired pulse ratio unchanged in all conditions, suggesting a non-beta 2* mediated effect. In the presence of MLA, nicotine decreased the mean spontaneous IPSC (sIPSC) frequency but increased their rise time, suggesting a non-alpha 7* AChR-mediated synaptic modulation. Also, in the presence of DH beta E, nicotine decreased both eIPSC rise and decay times. No receptors other than alpha 7* and beta 2* appear to be involved in the nicotine effect. Our results indicate that nicotine smoking concentrations modulate GABAergic synaptic currents through mixed pre- and post-synaptic mechanisms by activation of alpha 7* and beta 2* AChRs.