The electrophysiological actions of cocaine hydrochloride (COC) on med
ial prefrontal cortical (mpfc) and hippocampal dentate granule (DG) ne
urons were investigated in rat brain slices with intracellular recordi
ng techniques. The following parameters were measured: resting membran
e potential (RMP), spike threshold, spike firing adaptation, postspike
train afterhyperpolarization (AHP), excitatory postsynaptic potential
s (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 muM), whereas the amplitude of the postspike train afterhype
rpolarization (AHP) was reduced (an excitatory effect). In DG neurons,
1 muM COC caused a small depolarization. COC potentiated the EPSPs at
1 muM but attenuated EPSPs and IPSPs at 10-100 muM. The amplitude of
antidromically evoked EPSPs was also increased by 2.0 muM COC. At conc
entrations of 10 muM 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 neu
rotransmitters/modulators.