Cocaine actions on rat prefrontal cortical and hippocampal dentate granule neurons in vitro

The electrophysiological actions of cocaine hydrochloride (COC) on medial prefrontal cortical (mpfc) and hippocampal dentate granule (DG) neurons were investigated in rat brain slices with intracellular recording techniques. The following parameters were measured: resting membrane potential (RMP), spike threshold, spike firing adaptation, postspike train afterhyperpolarization (AHP), excitatory postsynaptic potentials (EPSPs), and inhibitory postsynaptic potentials (IPSPs). In the mpfc, COC appeared to have both inhibitory and excitatory effects. In the majority of cells examined, the EPSP amplitude was attenuated by COC (200 nM-20 microM), whereas the amplitude of the postspike train afterhyperpolarization (AHP) was reduced (an excitatory effect). In DG neurons, 1 microM COC caused a small depolarization. COC potentiated the EPSPs at 1 microM but attenuated EPSPs and IPSPs at 10-100 microM. The amplitude of antidromically evoked EPSPs was also increased by 20 microM COC. At concentrations of 10 microM and greater, COC increased spike threshold. It is concluded that COC actions on mpfc and DG neurons are both excitatory and inhibitory and that these effects may be mediated by multiple neurotransmitters/modulators.