Enkephalin enhances responsiveness to perforant path input while decreasing spontaneous activity in the dentate gyrus

The opioid peptide [D-Ala2-Met5]-enkephalin-amide (DAMEA) was electrophoretically applied to the dentate gyrus in vivo to investigate opioid effects on evoked responsiveness to perforant path input and on spontaneous granule cell activity. DAMEA increased the amplitude of population spikes evoked by stimulation of the perforant path, and decreased sequential (recurrent or feed-forward) inhibition as determined by a paired-pulse paradigm. However, DAMEA concurrently inhibited spontaneous activity of individual granule cells. The effects of DAMEA on population and unit responses were antagonized by intravenous naloxone. These results confirm previous findings of opioid enhanced responsiveness to perforant path input and decreased sequential inhibition, but demonstrate a paradoxical inhibition of spontaneous unit activity by opioids in the granule cell layer.