Dopamine (DA) has been reported to depolarize neurons in the prefronta
l cortex (PFC). To further characterize this effect of DA, we made who
le cell, recordings from PFC pyramidal cells in rat brain slices. As r
eported previously, DA depolarized most PFC cells tested. This effect
of DA was concentration-dependent and persisted in the presence of syn
aptic blockade, indicating a direct effect of DA on the recorded cell.
During DA-induced depolarization, PFC neurons consistently showed an
increase in excitability, suggesting that the depolarization is not di
rectly related to DA-induced inhibition of PFC neurons previously obse
rved in vivo. Surprisingly, the effect of DA was not mimicked or block
ed by several commonly used DA agonists and DA antagonists. The alpha
and beta antagonists phentolamine and alprenolol and the atypical anti
psychotic drug clozapine also showed no significant effect on DA-induc
ed depolarization. These results suggest that DA-induced depolarizatio
n may be mediated by a nonspecific mechanism. However, it remains poss
ible that there exists a new type of DA receptors in the PFC not sensi
tive to classical DA agonists and antagonists, particularly given the
fact that DA applied in the same manner depolarized only PFC neurons b
ut not those in the striatum or the substantia nigra. (C) 1997 Wiley-L
iss, Inc.