TY - JOUR
T1 - Relationship of μ- and δ-opioid receptors to GABAergic neurons in the central nervous system, including antinociceptive brainstem circuits
AU - Kalyuzhny, Alexander E.
AU - Wessendorf, Martin W.
PY - 1998/3/23
Y1 - 1998/3/23
N2 - Inhibition of neurons containing γ-aminobutyric acid (GABA) may underlie some of the excitatory effects of opioids in the central nervous system (CNS). In the present study, we examined the relationship of the cloned μ- and δ-opioid receptors (MOR1 and DOR1, respectively) to GABAergic neurons in brain and spinal cord. This was done by combining immunofluorescent staining for MOR1 and DOR1 with that for GABA or glutamic acid decarboxylase (GAD); fluorescent retrograde tract-tracing was used in some cases to identify neurons with particular projections. In rats, cells double labeled for GABA and MOR1 were observed in layers II-VI of the parietal cortex and in layers II-IV of the piriform cortex. In the hippocampus, double labeling was observed in the dentate gyrus and in regions CA1 and CA3. Double labeling was very prominent in the striatum and in the reticular nucleus of the thalamus; it was also observed in other portions of the diencephalon. However, double labeling for GABA and MOR1 was never observed in the cerebellar cortex. Cells double labeled for GABA and MOR1 were common in the periaqueductal gray (PAG) and the medial rostral ventral medulla (RVM) of both rats and monkeys, suggesting that involvement of GABAergic neurons with supraspinal opioid antinociception may extend to primates. In the RVM of rats, many of those double-labeled neurons were retrogradely labeled from the dorsal spinal cord. In contrast, double- labeled neurons in the PAG were almost never retrogradely labeled from the RVM. No unequivocal examples of double labeling for DOR1 and GAD were found in any region of the CNS that we examined in either rats or monkeys. However, GABAergic neurons were often supposed by DOR1 immunoreactive varicosities. Our findings suggest that activation of μ-opioid receptors directly modulates the activity of GABAergic neurons throughout the CNS, including neurons involved in the supraspinal component of opioid analgesia. In contrast, δ-opioid receptors appear to be positioned to modulate the activity of GABAergic neurons indirectly.
AB - Inhibition of neurons containing γ-aminobutyric acid (GABA) may underlie some of the excitatory effects of opioids in the central nervous system (CNS). In the present study, we examined the relationship of the cloned μ- and δ-opioid receptors (MOR1 and DOR1, respectively) to GABAergic neurons in brain and spinal cord. This was done by combining immunofluorescent staining for MOR1 and DOR1 with that for GABA or glutamic acid decarboxylase (GAD); fluorescent retrograde tract-tracing was used in some cases to identify neurons with particular projections. In rats, cells double labeled for GABA and MOR1 were observed in layers II-VI of the parietal cortex and in layers II-IV of the piriform cortex. In the hippocampus, double labeling was observed in the dentate gyrus and in regions CA1 and CA3. Double labeling was very prominent in the striatum and in the reticular nucleus of the thalamus; it was also observed in other portions of the diencephalon. However, double labeling for GABA and MOR1 was never observed in the cerebellar cortex. Cells double labeled for GABA and MOR1 were common in the periaqueductal gray (PAG) and the medial rostral ventral medulla (RVM) of both rats and monkeys, suggesting that involvement of GABAergic neurons with supraspinal opioid antinociception may extend to primates. In the RVM of rats, many of those double-labeled neurons were retrogradely labeled from the dorsal spinal cord. In contrast, double- labeled neurons in the PAG were almost never retrogradely labeled from the RVM. No unequivocal examples of double labeling for DOR1 and GAD were found in any region of the CNS that we examined in either rats or monkeys. However, GABAergic neurons were often supposed by DOR1 immunoreactive varicosities. Our findings suggest that activation of μ-opioid receptors directly modulates the activity of GABAergic neurons throughout the CNS, including neurons involved in the supraspinal component of opioid analgesia. In contrast, δ-opioid receptors appear to be positioned to modulate the activity of GABAergic neurons indirectly.
KW - Analgesia
KW - Confocal microscopy
KW - Opiates
KW - Pain
KW - Retrograde tract tracing
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U2 - 10.1002/(SICI)1096-9861(19980323)392:4<528::AID-CNE9>3.0.CO;2-2
DO - 10.1002/(SICI)1096-9861(19980323)392:4<528::AID-CNE9>3.0.CO;2-2
M3 - Article
C2 - 9514515
AN - SCOPUS:0032536895
SN - 0021-9967
VL - 392
SP - 528
EP - 547
JO - Journal of Comparative Neurology
JF - Journal of Comparative Neurology
IS - 4
ER -