Characterization of dopamine-induced depolarization of prefrontal cortical neurons.
Dopamine (DA) has been reported to depolarize neurons in the prefrontal cortex (PFC). To further characterize this effect of DA, we made whole cell recordings from PFC pyramidal cells in rat brain slices. As reported previously, DA depolarized most PFC cells tested. This effect of DA was concentration-dependent and persisted in the presence of synaptic 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 directly related to DA-induced inhibition of PFC neurons previously observed in vivo. Surprisingly, the effect of DA was not mimicked or blocked by several commonly used DA agonists and DA antagonists. The alpha and beta antagonists phentolamine and alprenolol and the atypical antipsychotic drug clozapine also showed no significant effect on DA-induced depolarization. These results suggest that DA-induced depolarization may be mediated by a nonspecific mechanism. However, it remains possible that there exists a new type of DA receptors in the PFC not sensitive to classical DA agonists and antagonists, particularly given the fact that DA applied in the same manner depolarized only PFC neurons but not those in the striatum or the substantia nigra.
Shi
W X
WX
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510, USA. wei-xing.shi@yale.edu
Zheng
P
P
Liang
X F
XF
Bunney
B S
BS
D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology* / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004298:Dopamine