Endogenous gonadal hormones modulate behavioral and neurochemical responses to acute and chronic cocaine administration
Endogenous gonadal hormones modulate behavioral and neurochemical responses to acute and chronic cocaine administration
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DOI：
10.1016/s0006-8993(02)02807-x
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发表时间：
2002-07-26
期刊：
影响因子：
2.9
通讯作者：
Quiñones-Jenab, V
中科院分区：
文献类型：
--
作者：
Chin, J;Sternin, O;Quiñones-Jenab, V
最近的证据表明，可卡因的行为反应存在性别差异。此外，生殖性腺激素(雌激素、孕激素和睾酮)进一步参与了可卡因诱导的某些改变的调节。为了更好地了解性别差异以及性腺激素在可卡因诱导的运动和刻板行为中的作用，将正常和性腺切除的Fischer雄性和雌性大鼠随机分为两组，分别给予慢性可卡因(15 mg/kg)或生理盐水治疗14天，然后再给予挑战给药(最后一次注射可卡因/生理盐水后7天)。分别在第1、7、14天以及戒断/激发可卡因后测量运动(行走和站立)和刻板印象活动。总体而言，与任何其他组相比，完好的雌性大鼠对所有运动行为都表现出快速(在第7天获得)和更长时间(持续到激发剂量)的敏感化。相比之下，完整的男性只有在长期服用可卡因时才对这些运动活动产生敏感化，在戒断和药物挑战之后，对可卡因诱导的运动活动的敏感化不再存在。在雌性大鼠中，性腺切除影响了对可卡因的急性、亚急性、慢性和挑战反应后的活动活动，但不影响总体和饲养反应。另一方面，去势雄性大鼠在可卡因诱导的活动中受到影响，但不影响饲养活动。在完整雄性大鼠中，可卡因诱导的刻板印象活动在给药7天后迅速而持续地敏化，而去性腺的雄性大鼠只有在挑战可卡因给药后才对可卡因诱导的刻板印象活动敏感。尽管可卡因引起了刻板印象的活动，但在完整的雌性大鼠和去卵巢的雌性大鼠之间，以及在不同的可卡因给药时间内，没有观察到统计学上的显著差异。在可卡因刺激后，所有实验组的皮质酮水平都被诱导。此外，没有观察到可卡因代谢物苯甲酰ecGonine水平的差异。与我们之前观察到的急性可卡因给药后相似，可卡因激发后，正常女性和男性的孕酮水平分别升高和睾酮水平下降。综上所述，内源性激素似乎参与了可卡因的行为激活和发展。(C)2002年，爱思唯尔科学公司出版。
Recent evidence demonstrates that there are sex differences in behavioral responses to cocaine. Further, reproductive gonadal hormones (estrogen, progesterone and testosterone) have been further implicated in mediating some of the cocaine-induced alterations. To better understand sex differences and the role of gonadal hormones in cocaine-induced locomotor and stereotypic behavior, intact and gonadectomized male and female Fischer rats were randomly assigned to either chronic cocaine (15 mg/kg) or saline treatments for 14 days followed by a challenge administration (7 days after the last cocaine/saline administration). Locomotor (ambulatory and rearing) and stereotypic activities were measured on days 1, 7 and 14 as well as after withdrawal/challenge with cocaine. Overall, intact female rats consistently showed a rapid (acquired by day 7) and longer lasting (persistent through the challenge dose) sensitization for all locomotor behaviors than any of the other groups. In contrast, intact males developed sensitization of these locomotor activities only in response to chronic cocaine administration, and after withdrawal and drug challenge the sensitization to cocaine-induced locomotor activity was no longer present. In female rats, gonadectomy affected ambulatory activity but not total and rearing responses after acute, sub-acute, chronic and challenge response to cocaine. On the other hand, castrated male rats were affected in cocaine-induced ambulatory activity but not rearing activity. In intact male rats, cocaine-induced stereotypic activity was rapidly and persistently sensitized after 7 days of cocaine administration, where gonadectomized male rats developed sensitization to cocaine-induced stereotypic activity only after a challenge cocaine administration. Although cocaine induced stereotypic activity, no statistically significant differences were observed between intact and ovariectomized female rats or throughout the different lengths of cocaine administration. After a challenge of cocaine, corticosterone levels were induced in all experimental groups. Moreover, no differences in levels of benzoylecgonine, a cocaine metabolite, were observed. Similar to our previous observations after acute cocaine administration, after challenge of cocaine, an increase in progesterone and a decrease in testosterone levels were observed in intact females and males, respectively. In summary, endogenous hormones seem to be involved in the behavioral activation and development of sensitization to cocaine. (C) 2002 Published by Elsevier Science B.V.