Roles of two subtypes of corticotrophin-releasing factor receptor in the corticostriatal long-term potentiation under cocaine withdrawal condition.
The roles of two subtypes of corticotrophin-releasing factor (CRF) receptor in corticostriatal synaptic plasticity under cocaine withdrawal condition were examined in this study. Neither the resting membrane potential and input resistance of striatal neurons nor the long-term potentiation (LTP) of corticostriatal slices were affected by cocaine withdrawal. CRF dose-dependently enhanced in vitro corticostriatal LTP in rats from both cocaine-withdrawal and saline-control groups. Yet, the enhancement of corticostriatal LTP by CRF (20, 40, 80 nM) was significantly greater in the cocaine-withdrawal group than in the control group. CRF(1)-selective antagonist (NBI 27914, 100 nM) attenuated the CRF-induced enhancement of corticostriatal LTP in both groups, whereas the CRF(2)-selective antagonist (astression2B, 100 nM) attenuated the enhanced corticostriatal LTP only in the cocaine-withdrawal group. Importantly, urocortin2 (a CRF(2)-selective agonist, 40 nM) selectively increased corticostriatal LTP in the cocaine-withdrawal group, but not in the saline controls. The urocortin2-induced enhancement of LTP was totally blocked by astression2B (100 nM). These results suggest that the CRF system modulate neuroadaptive changes in the corticostriatal circuit during cocaine withdrawal, and the CRF(2) in this area mediate an important mechanism that contributes to the relapse of cocaine addiction.
Guan
Xiaowei
X
Department of Pharmacology, Nanjing Medical University, Nanjing, China.
Wang
Lina
L
Chen
Chun-Lin
CL
Guan
Yun
Y
Li
Shengnan
S
D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D003042:Cocaine / Q000009:adverse effects*; D003342:Corpus Striatum / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004594:Electrophysiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology* / Q000523:psychology; D013569:Synapses / Q000502:physiology; D054832:Urocortins / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine