Effects of the delta-opioid agonist, [D-Pen2,D-Pen5]-enkephalin, on fetal lamb EEG.

Opiates are known to exert biphasic effects on level of arousal, with excitation at low doses and depression at higher doses. It has been suggested that this dual excitatory and depressant actions of opiates may be mediated by different receptor subtypes. We have previously shown that activation of mu 1-opioid receptors evoked EEG activation in the fetal lamb. The purpose of the present study was to quantitate the effects of DPDPE, a highly selective delta-opioid agonist, on fetal EEG. When infused ICV (4.6-154 nmol/h), DPDPE elicited dose-dependent activation of fetal EEG, with a reduction in power distribution in the delta (1-4 Hz) band, and an increase in the beta (15-32 Hz) band. This activation was reflected by an increase in the spectral edge frequency. This EEG activation was greatly attenuated at DPDPE doses greater than 154 nmol/h, resulting in a U-shaped dose-response curve. The EEG activation was completely blocked by naloxone or naltrindole (delta antagonist), but not by naloxonazine (mu 1 antagonist). These results indicate that the activation of delta-opioid receptors will evoke EEG activation in the fetal lamb.