Constitutive activation of kappa opioid receptors at ventral tegmental area inhibitory synapses following acute stress
- Brown University, United States
- University of Wyoming, United States
- University of Wyoming, School of Pharmacy, United States
Figures
Figure 1 with 1 supplement
norBNI rescues LTPGABA through activation of JNK.
(A) Summary data showing the blockade of LTPGABA after stress. (B) Comparison of the magnitude of LTPGABA10–15 min after SNAP application. (IPSC amplitudes, control: 140 ± 5% of baseline values, n = …
Figure 1—figure supplement 1
Inhibition of JNK does not affect LTPGABA or its block by stress in the absence of norBNI.
(A) Summary data showing that LTPGABA is expressed in slices from naïve animals in the presence of the JNK inhibitor SP600125 (20 µM). Average magnitude of LTPGABA10–15 min after SNAP = 144 ± 13% of …
Figure 2 with 1 supplement
The neutral antagonist 6β-naltrexol fails to rescue LTPGABA in slices from stressed animals.
(A) Schematic of norBNI and 6β-naltrexol inhibition of κOR signaling. (B) Experimental design. (C) Representative experiment showing that bath application of norBNI (100 nM) rescues LTPGABA in a …
Figure 2—figure supplement 1
6β-naltrexol does not affect basal inhibitory synaptic transmission but does block κORs.
(A) Summary data showing that 6β-naltrexol (10 µM) does not affect basal inhibitory transmission in cells from control or stressed rats. Normalized IPSC amplitude 5–10 min after 6β-naltrexol: …
Figure 3
6β-naltrexol rescues LTPGABA when administered pre-stress, but not post-stress.
(A) Experimental design. (B) Representative experiment showing that a cell from a vehicle-treated stressed animal does not exhibit LTPGABA. (C) Representative experiment showing that a cell from an …
Figure 4
Single treatment with a κOR agonist leads to prolonged blockade of LTPGABA.
(A) Experimental design. (B) Representative experiment showing that a cell from a saline-treated animal exhibits LTPGABA. (C) Representative single experiment showing a cell prepared 24 hr after a …
Figure 5
κORs at VTA excitatory synapses are not constitutively activated by stress.
(A) Representative experiment showing that norBNI (100 nM) does not potentiate excitatory synapses on Ih+ VTA neurons in a slice prepared from a control animal. (B) Representative experiment showing …
Figure 6
Post-stress rescue of reinstatement by norBNI but not 6β-naltrexol.
(A) Experimental design. (B) Lever pressing during the final extinction session (white bar) and reinstatement session (colored bar). Saline (black): last extinction session: 6.4 ± 1.7 lever presses; …
Figure 7
Constitutive activation of κORs by stress.
(A) During stress, dynorphin binding to the κOR triggers a shift to a constitutively active state. By blocking dynorphin binding, both norBNI and 6β-naltrexol prevent the loss of LTPGABA during this …
