Anatomical evidence for presynaptic modulation by the delta opioid receptor in the ventrolateral periaqueductal gray of the rat

The delta opioid receptor (DOR) modulates nociception and blood pressure in the periaqueductal gray (PAG). To examine the cellular basis for DOR effec ts, the ultrastructural distribution of DOR immunoreactivity was examined i n the caudal ventrolateral PAG. DOR immunoreactivity was located predominan tly in axon terminals that formed asymmetric (excitatory-type) synaptic con tacts. However, rather then localized to the plasma membrane of synaptic bo utons, immunolabeling for the DOR was intracellular, often associated with large dense-core vesicles. This finding suggests that dense-core vesicles m ay play a role in targeting the DOR, as vesicle fusion would shift the dist ribution of the DOR to the plasma membrane. To investigate the neural circu its in which DOR may function, dual-immunolabeling was used to determine th e relationship of the DOR to an endogenous ligand, enkephalin, and to a pot ential target, GABAergic neurons. Approximately a third (38 of 127) of DOR containing axons had enkephalin immunoreactivity, indicating DOR may act in part as a presynaptic autoreceptor. Although single axon terminals contain ing immunoreactivity for both DOR and GABA were not detected, some DOR-immu nolabeled axon terminals (26 of 86) contacted soma or dendrites containing GABA. These data suggest that the DOR may act in part as an autoreceptor to regulate synaptic input to GABAergic as well as non-GABAergic PAG neurons. Furthermore, the exposure of the DOR to the extracellular space may be con tingent upon dense-core vesicle fusion with the plasma membrane. J. Comp. N eurol. 430: 200-208, 2001. (C) 2001 Wiley-Liss, Inc.