Dimatelis J J, Russell V A, Stein D J, Daniels W M
Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town, South Africa, 7925,
Metab Brain Dis. 2014 Jun;29(2):433-9. doi: 10.1007/s11011-014-9481-z. Epub 2014 Jan 11.
Stress has been suggested to predispose individuals to drug abuse. The early life stress of maternal separation (MS) is known to alter the response to drugs of abuse later in life. Exposure to either stress or methamphetamine has been shown to alter neurotrophic factors in the brain. Changes in neurotrophin levels may contribute to the underlying molecular mechanisms responsible for drug use- and stress-induced behaviours. The purpose of the present study was to investigate the individual effects of MS and methamphetamine administration during adolescence and the combined effects of both stressors on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the dorsal and ventral hippocampus (HC) in adulthood. Methamphetamine administration (1 mg/kg, daily from postnatal day (PND) 33 to 36 and from PND 39 to 42), MS and the combination of the two stressors resulted in decreased BDNF levels in both the dorsal and ventral HC. MS decreased NGF levels in the ventral HC which was restored by methamphetamine administration in adolescence. In the dorsal HC, NGF remained unaltered by either stressor alone or in combination. We propose that the restoration of NGF levels in the ventral HC may reflect a possible compensatory mechanism in response to methamphetamine exposure in adolescence following the early life stress of MS.
有研究表明，压力会使个体更容易滥用药物。众所周知，早年的母婴分离应激（MS）会改变个体在日后生活中对滥用药物的反应。暴露于压力或甲基苯丙胺中已被证明会改变大脑中的神经营养因子。神经营养素水平的变化可能有助于解释导致药物使用和应激诱导行为的潜在分子机制。本研究的目的是调查青春期母婴分离应激和甲基苯丙胺给药的个体影响，以及这两种应激源对成年大鼠背侧和腹侧海马体（HC）中脑源性神经营养因子（BDNF）和神经生长因子（NGF）水平的联合影响。甲基苯丙胺给药（从出生后第33天至36天以及从出生后第39天至42天，每天1mg/kg）、母婴分离应激以及这两种应激源的联合作用均导致背侧和腹侧海马体中BDNF水平降低。母婴分离应激降低了腹侧海马体中的NGF水平，而青春期甲基苯丙胺给药可使其恢复。在背侧海马体中，单独或联合使用任何一种应激源都不会改变NGF水平。我们认为，腹侧海马体中NGF水平的恢复可能反映了在经历母婴分离应激这种早年生活压力后，对青春期甲基苯丙胺暴露的一种可能的代偿机制。
