Morphine and DAMGO produce an opposite effect on presynaptic glutamate release via different downstream pathways of μ opioid receptors in the basolateral amygdala

The basolateral amygdala (BLA) is the major amygdaloid nucleus distributed with μ opioid receptors. The afferent input from the BLA to the central nucleus of the amygdala (CeA) is considered important for opioid analgesia. However, little is known about the effect of μ opioids on synaptic transmission in the BLA. In this study, we examined the effect of μ opioid receptor stimulation on the inhibitory and excitatory synaptic inputs to CeA-projecting BLA neurons. BLA neurons were retrogradely labeled with a fluorescent tracer injected into the CeA of rats. Whole cell voltage-clamp recordings were performed on labeled BLA neurons in brain slices. The specific μ opioid receptor agonist, (d-Ala2, N-Me-Phe4,Gly5-ol)-enkephalin (DAMGO, 1 μM), significantly reduced the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in 77% of cells tested. DAMGO also significantly decreased the peak amplitude of evoked IPSCs in 75% of cells examined. However, DAMGO did not significantly alter the frequency of mEPSCs or the peak amplitude of evoked EPSCs in 90% and 75% of labeled cells, respectively. Bath application of the Kv channel blockers, 4-AP (Kv1.1, 1.2, 1.3, 1.5, 1.6, 3.1, 3.2), α-dendrotoxin (Kv1.1, 1.2, 1.6), dendrotoxin-K (Kv1.1), or tityustoxin-Kα (Kv1.2) each blocked the inhibitory effect of DAMGO on mIPSCs. Double immunofluorescence labeling showed that some of the immunoreactivities of Kv1.1 and Kv1.2 were colocalized with synaptophysin in the BLA. This study provides new information that activation of presynaptic μ opioid receptors primarily attenuates GABAergic synaptic inputs to CeA-projecting neurons in the BLA through a signaling mechanism involving Kv1.1 and Kv1.2 channels.

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Functional Interaction Between TRPV1 and μ-Opioid Receptors in the Descending Antinociceptive Pathway Activates Glutamate Transmission and Induces Analgesia

Journal of Neurophysiology ◽

10.1152/jn.91225.2008 ◽

2009 ◽

Vol 101 (5) ◽

pp. 2411-2422 ◽

Cited By ~ 40

Author(s):

Sabatino Maione ◽

Katarzyna Starowicz ◽

Luigia Cristino ◽

Francesca Guida ◽

Enza Palazzo ◽

...

Keyword(s):

Opioid Receptors ◽

Glutamate Release ◽

Receptor Activation ◽

Rostral Ventromedial Medulla ◽

Neuron Activity ◽

Opioid Receptor Antagonists ◽

Ventromedial Medulla ◽

Output Neurons ◽

Μ Opioid Receptors ◽

Μ Receptor

The transient receptor potential vanilloid-1 (TRPV1) receptor is involved in peripheral and spinal nociceptive processing and is a therapeutic target for pain. We have shown previously that TRPV1 in the ventrolateral periaqueductal gray (VL-PAG) tonically contributes to brain stem descending antinociception by stimulating glutamate release into the rostral ventromedial medulla and off neuron activity. Because both opioid and vanilloid systems integrate and transduce pain sensation in these pathways, we studied the potential interaction between TRPV1 and μ-opioid receptors in the VL-PAG–rostral ventromedial medulla (RVM) system. We found that the TRPV1 agonist, capsaicin, and the μ-receptor agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin, when coadministered into the ventrolateral-PAG at doses nonanalgesic per se, produce 1) antinociception in tests of thermal nociception; 2) stimulation of glutamate release into the RVM; and 3) inhibition of on neuron activity in the RVM. These effects were all antagonized by the TRPV1 and opioid receptor antagonists 5′-iodo-resiniferatoxin and naloxone, respectively, thus suggesting the existence of a TRPV1–μ-opioid interaction in the VL-PAG–RVM system. By using double immunofluorescence techniques, we found that TRPV1 and μ-opioid receptors are coexpressed in several neurons of the VL-PAG. These findings suggest that μ-receptor activation not only acts on inhibitory neurons to disinhibit PAG output neurons but also interacts with TRPV1 activation at increasing glutamate release into the RVM, possibly by acting directly on PAG output neurons projecting to the RVM.

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