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. Author manuscript; available in PMC: 2024 May 15.
Published in final edited form as: Neuropharmacology. 2024 Feb 15;248:109866. doi: 10.1016/j.neuropharm.2024.109866

Figure 6. Hypothetical mechanism of action of NOP agonist and antagonist on regulating the spontaneous VTA DA firing discharge.

Figure 6.

NOP receptor agonists produce a direct postsynaptic hyperpolarization of VTA DA neurons and a presynaptic inhibition of GABA transmission. The activation of NOP receptors located on DA neurons strongly prevails on NOP-mediated reduction of GABA transmission, resulting in direct inhibition of DA activity. NOP receptor antagonists leads to inhibition of VTA DA activity through a GABARs mediated mechanisms; in presence of GABARs antagonists the effect is abolished. Potential mechanism of NOP antagonists: (1) removal of N/OFQ-mediated endogenous inhibition of GABA transmission; (2) increased activity and neurotransmitter release from presynaptic GABA neurons; (3) enhanced activation of postsynaptic GABARs in VTA DA neurons resulting in a decreased firing activity of these neurons.