Opioid effects on activation of neurons in the medial prefrontal cortex

1. The effects of opioids have been characterized in portions of the neural circuitry proposed to underly the development and maintenance of addiction. One possible mechanism is modulation of function of endogenous transmitters. 2. Cells in the prefrontal cortex, a brain area involved in cognitive function and processes relevant to addiction, are described that exhibit morphine-associated attenuation of activation response to glutamate but not acetylcholine. 3. The predominantly excitatory response of prefrontal cortical cells to local application of glutamate and acetylcholine were differentially modified by systemic and local application of opioids. 4. Local mu opioid effects mimic those of systemic morphine to a more limited degree. 5. Morphine attenuates the response of prefrontal cortical cells to activation of excitatory afferents from the mediodorsal thalamus, and to a lesser degree, from the basolateral amygdala and the hippocampus. 6. Morphine modulation of prefrontal excitatory activation is naloxone-reversible.