Mello N K, Mendelson J H, Drieze J M, Teoh S K, Kelly M L, Sholar J W
Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, Belmont, Massachusetts.
J Pharmacol Exp Ther. 1994 Sep;270(3):1110-20.
The effects of dopamine on regulation of prolactin secretion were studied in female rhesus monkeys before cocaine exposure and again after 2 months to 2.7 years of daily cocaine self-administration. During chronic cocaine exposure, basal prolactin levels increased by 227 to 350% above drug-free control levels (P < .05). On each endocrine study day, three successive 80-min dopamine infusions (10 micrograms/kg/min i.v.) were alternated with 20-min interruptions of dopamine infusions to assess the degree of prolactin suppression and the magnitude of postdopamine prolactin increases. Dopamine significantly reduced prolactin below base-line levels within 60 to 80 min under all conditions (P < .05-.01). In four drug-naive follicular phase females, postdopamine increases in prolactin never exceeded predopamine base-line levels of 6.2 (+/- 1.8) ng/ml. After an average of 74 days of cocaine self-administration [3.7 (+/- 0.11) mg/kg/day], the postdopamine prolactin increases were significantly higher than during drug-free control conditions (P < .01) and reached hyperprolactinemic levels of 57.6 ng/ml. After an average of 300 days of cocaine self-administration [6.5 (+/- 0.06) mg/kg/day], postdopamine prolactin increases peaked at 339% above predopamine basal prolactin levels. After an average of 433 days of cocaine self-administration [6.45 (+/- 0.08) mg/kg/day] postdopamine prolactin increases remained significantly higher (P < .01) than during drug-free conditions. A similar pattern of postdopamine prolactin increases to hyperprolactinemic levels (ranging from 44.5 to 141.2 ng/ml) also were measured in two other females studied after 19 to 20 months of cocaine self-administration [6.21 (+/- 0.11) and 7.49 (+/- 0.17) mg/kg/day]. After 2.7 years of cocaine self-administration, one monkey developed persistent hyperprolactinemia and basal prolactin levels averaged 326 ng/ml after 89 days of cocaine abstinence. These data suggest that the prolactin secretory response to dopamine perturbation may provide a sensitive index of changes in dopaminergic regulation of prolactin during chronic cocaine exposure.
在雌性恒河猴接触可卡因之前以及在每天自我给药可卡因2个月至2.7年后，研究了多巴胺对催乳素分泌调节的影响。在慢性可卡因接触期间，基础催乳素水平比无药对照水平高出227%至350%（P<.05）。在每个内分泌研究日，连续三次80分钟的多巴胺输注（静脉注射10微克/千克/分钟）与20分钟的多巴胺输注中断交替进行，以评估催乳素抑制程度和多巴胺后催乳素增加的幅度。在所有条件下，多巴胺在60至80分钟内将催乳素显著降低至基线水平以下（P<.05-.01）。在四名未接触过药物的卵泡期雌性中，多巴胺后催乳素的增加从未超过多巴胺前基线水平6.2（±1.8）纳克/毫升。在平均74天的可卡因自我给药[3.7（±0.11）毫克/千克/天]后，多巴胺后催乳素的增加显著高于无药对照条件下（P<.01），并达到高催乳素血症水平57.6纳克/毫升。在平均300天的可卡因自我给药[6.5（±0.06）毫克/千克/天]后，多巴胺后催乳素的增加达到比多巴胺前基础催乳素水平高出339%的峰值。在平均433天的可卡因自我给药[6.45（±0.08）毫克/千克/天]后，多巴胺后催乳素的增加仍显著高于无药条件下（P<.01）。在另外两名在19至20个月的可卡因自我给药[6.21（±0.11）和7.49（±0.17）毫克/千克/天]后进行研究的雌性中，也测量到了类似的多巴胺后催乳素增加至高催乳素血症水平（范围为44.5至141.2纳克/毫升）的模式。在2.7年的可卡因自我给药后，一只猴子出现了持续性高催乳素血症，在禁欲89天后基础催乳素水平平均为326纳克/毫升。这些数据表明，催乳素对多巴胺扰动的分泌反应可能为慢性可卡因接触期间多巴胺能对催乳素调节变化提供一个敏感指标。
