Wakeford Alison G P, Kochoian Brik, Siebert Erin R, Katznelson Sarah, Morin Elyse L, Howell Brittany R, McCormack Kai M, Nader Michael A, Sanchez Mar M, Howell Leonard L
Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd NE, Atlanta, GA, 30329, USA.
Department of Psychiatry & Behavioral Sciences, Emory University, 12 Executive Park Dr NE #200, Atlanta, GA, 30329, USA.
Psychopharmacology (Berl). 2020 Dec;237(12):3583-3589. doi: 10.1007/s00213-020-05637-2. Epub 2020 Aug 21.
It is critical to identify potential risk factors, such as a history of early life stress (ELS), that may confer specific vulnerabilities to increased drug intake.
In this study, we examined whether male and female rhesus monkeys with a history of ELS (infant maltreatment; MALT) demonstrated significantly greater cocaine intake compared with controls.
Monkeys were trained to self-administer cocaine during 4-h sessions at a peak dose (0.003-0.1 mg/kg/infusion; extended access, "EA peak") and a dose of 0.1 mg/kg/infusion (EA 0.1) of cocaine. These data were compared with data obtained previously in monkeys trained during 1-h limited access (LA) sessions at the same peak dose of cocaine used here (Wakeford et al. Psychopharmacology, 236:2785-2796, 2019).
Monkeys significantly increased total number of infusions earned in EA compared with LA, but total session response rates significantly decreased in EA compared with LA. There was no evidence of escalation in drug intake when we compared response rates to obtain the first 20 cocaine infusions between LA and EA peak conditions. Moreover, there was no evidence of escalation in drug intake during an additional 7 weeks of self-administration at 0.1 mg/kg/injection.
The current study expands on previous reports demonstrating that rhesus macaques did not escalate cocaine intake under the experimental conditions employed and extended these findings by using a unique population of nonhuman primates with a history of infant MALT to test the hypothesis that ELS is a risk factor for escalation of cocaine intake in nonhuman primates. There was no clear evidence of escalation in cocaine intake as a consequence of ELS.
识别潜在风险因素至关重要,例如早期生活压力(ELS)史,其可能导致药物摄入量增加的特定易感性。
在本研究中,我们检验了有ELS史(婴儿期虐待;MALT)的雄性和雌性恒河猴与对照组相比是否表现出显著更高的可卡因摄入量。
训练猴子在4小时的实验时段内自行给药可卡因,分别给予峰值剂量(0.003 - 0.1毫克/千克/次输注;延长给药时间,“EA峰值”)和0.1毫克/千克/次输注剂量(EA 0.1)的可卡因。将这些数据与之前在1小时有限给药时间(LA)实验时段训练的猴子在相同可卡因峰值剂量下获得的数据进行比较(Wakeford等人,《精神药理学》,236:2785 - 2796,2019)。
与LA相比,猴子在EA实验中获得的总输注次数显著增加,但与LA相比,EA实验中的总实验时段反应率显著降低。当我们比较在LA和EA峰值条件下获得前20次可卡因输注的反应率时,没有证据表明药物摄入量增加。此外,在以0.1毫克/千克/次注射剂量进行额外7周的自行给药期间,也没有证据表明药物摄入量增加。
本研究扩展了先前的报告,表明恒河猴在所用实验条件下不会增加可卡因摄入量,并通过使用具有婴儿期MALT史的独特非人灵长类动物群体扩展了这些发现,以检验ELS是非人灵长类动物可卡因摄入量增加的风险因素这一假设。没有明确证据表明ELS会导致可卡因摄入量增加。