AbstractThere is evidence to suggest that medium spiny neurons (MSNs) in the nucleus accumbens (NAS) should be sensitive to opiate compounds. However, neuronal responses in the NAS evoked by fimbria stimulation (F‐D) are insensitive to systemically or iontophoretically administered morphine. The hypothesis of this study was that fimbria‐evoked NAS responses may fail to demonstrate sensitivity to morphine because they are under tonic opioid inhibition and can't be further inhibited by opiates. If correct, then pharmacological inhibition of opioid actions on these NAS neuronal responses should result in an increase of response to fimbria stimulation. The effects of systemic and iontophoretic administrations of naloxone on NAS responses evoked by fimbria stimulation were observed. Systemically and locally administered naloxone selectively increased the excitability of accumbens single‐unit responses to fimbria stimulation. Conversely, systemic or iontophoretic administration of morphine was without effect on the same types of NAS responses. These observations are consistent with the hypothesis that a tonic opioid inhibition may regulate this pathway. In contrast, naloxone and morphine effect other NAS circuit responses differently than F‐D NAS responses. In some cases naloxone and morphine tests have been conducted on different evoked responses from the same neuron. Those results have shown that different responses from the same cell may be differentially affected. Consequently, opioid modulation of activity in the NAS is probably pathway‐specific rather than neuron‐specific. Synapse 41:71–85, 2001. © 2001 Wiley‐Liss, Inc.