The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats
The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats
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DOI：
10.1523/jneurosci.18-14-05529.1998
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发表时间：
1998-07-15
影响因子：
5.3
通讯作者：
Stewart, J
中科院分区：
文献类型：
--
作者：
Erb, S;Shaham, Y;Stewart, J
我们以前已经证明，足部电击应激和注射可卡因可使大鼠在长时间的无毒期后恢复寻找可卡因(Erb等人，1996年)。在这里，我们研究了脑促肾上腺皮质激素释放因子(CRF)和肾上腺激素皮质酮在应激和可卡因诱导的大鼠恢复寻找可卡因中的作用。采用CRF受体拮抗剂D-Phe CRF12-41侧脑室注射、肾上腺切除后和肾上腺切除加皮质酮替代后，研究足底电击应激和预先注射可卡因诱导大鼠再次寻找可卡因的能力。大鼠静脉注射可卡因(1.0 mg/kg/次)。每天3小时，持续10-14天，然后按熄灭时间表放置，在此期间用生理盐水代替可卡因。在间歇性足底电击(10min；0.5 mA)和预先注射生理盐水和可卡因(20 mg/kg，i.p)后进行恢复试验。足底电击恢复了在完整动物和皮质酮替代动物中寻找可卡因，但不在肾上腺切除动物中寻找可卡因。CRF受体拮抗剂D-Phe CRF12-41在完整动物和皮质酮替代动物身上测试的所有剂量都能阻止足底电击诱导的恢复。肾上腺切除和D-苯丙氨酸受体拮抗剂CRF12-41对注射可卡因的恢复作用影响最小。这些数据表明，大脑CRF在应激诱导中起着关键作用，但在可卡因诱导、恢复可卡因寻求过程中只起到调制作用。此外，数据显示，尽管通过足电击应激恢复可卡因寻找需要最低的基础皮质酮水平，但应激诱导的皮质酮增加在这一效应中不起作用。
We have shown previously that footshock stress and priming injections of cocaine reinstate cocaine seeking in rats after prolonged drug-free periods (Erb et al., 1996). Here we examined the role of brain corticotropin-releasing factor (CRF) and the adrenal hormone corticosterone in stress- and cocaine-induced reinstatement of cocaine seeking in rats. The ability of footshock stress and priming injections of cocaine to induce relapse to cocaine seeking was studied after intracerebroventricular infusions of the CRF receptor antagonist D-Phe CRF12-41, after adrenalectomy, and after adrenalectomy with corticosterone replacement. Rats were allowed to self-administer cocaine (1.0 mg/kg/infusion, i.v.) for 3 hr daily for 10-14 d and were then placed on an extinction schedule during which saline was substituted for cocaine. Tests for reinstatement were given after intermittent footshock (10 min; 0.5 mA) and after priming injections of saline and cocaine (20 mg/kg, i.p.). Footshock reinstated cocaine seeking in both intact animals and animals with corticosterone replacement but not in adrenalectomized animals. The CRF receptor antagonist D-Phe CRF12-41 blocked footshock-induced reinstatement at all doses tested in both intact animals and animals with corticosterone replacement. Reinstatement by priming injections of cocaine was only minimally attenuated by adrenalectomy and by pretreatment with D-Phe CRF12-41. These data suggest that brain CRF plays a critical role in stress-induced, but only a modulatory role in cocaine-induced, reinstatement of cocaine seeking. Furthermore, the data show that although reinstatement of cocaine seeking by footshock stress requires minimal, basal, levels of corticosterone, stress-induced increases in corticosterone do not play a role in this effect.