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Stress induces reinstatement of extinguished cocaine conditioned place preference by a sequential signaling via neuropeptide S, orexin, and endocannabinoid
Author(s) -
Chou YuHsien,
Hor Chia Chun,
Lee Ming Tatt,
Lee HsinJung,
Guerrini Remo,
Calo Girolamo,
Chiou LihChu
Publication year - 2021
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12971
Subject(s) - ventral tegmental area , conditioned place preference , orexin , endocannabinoid system , orexin receptor , orexin a , lateral hypothalamus , endocrinology , medicine , chemistry , neuropeptide , context (archaeology) , pharmacology , dopamine , dopaminergic , receptor , hypothalamus , biology , paleontology
Neurons containing neuropeptide S (NPS) and orexins are activated during stress. Previously, we reported that orexins released during stress, via orexin OX 1 receptors (OX 1 Rs), contribute to the reinstatement of cocaine seeking through endocannabinoid/CB 1 receptor (CB 1 R)‐mediated dopaminergic disinhibition in the ventral tegmental area (VTA). Here, we further demonstrated that NPS released during stress is an up‐stream activator of this orexin‐endocannabinoid cascade in the VTA, leading to the reinstatement of cocaine seeking. Mice were trained to acquire cocaine conditioned place preference (CPP) by context‐pairing cocaine injections followed by the extinction training with context‐pairing saline injections. Interestingly, the extinguished cocaine CPP in mice was significantly reinstated by intracerebroventricular injection ( i.c.v .) of NPS (1 nmol) in a manner prevented by intraperitoneal injection ( i.p .) of SHA68 (50 mg/kg), an NPS receptor antagonist. This NPS‐induced cocaine reinstatement was prevented by either i.p . or intra‐VTA microinjection ( i.vta .) of SB‐334867 (15 mg/kg, i.p . or 15 nmol, i.vta .) and AM 251 (1.1 mg/kg, i.p . or 30 nmol, i.vta .), antagonists of OX 1 Rs and CB 1 Rs, respectively. Besides, NPS (1 nmol, i.c.v .) increased the number of c‐Fos‐containing orexin neurons in the lateral hypothalamus (LH) and increased orexin‐A level in the VTA. The latter effect was blocked by SHA68. Furthermore, a 30‐min restraint stress in mice reinstated extinguished cocaine CPP and was prevented by SHA68. These results suggest that NPS is released upon stress and subsequently activates LH orexin neurons to release orexins in the VTA. The released orexins then reinstate extinguished cocaine CPP via an OX 1 R‐ and endocannabinoid‐CB 1 R‐mediated signaling in the VTA.